Levels of depression and self-esteem in women with cancer of the endometrium and cervix receiving chemotherapy treatment in Türkiye.

OBJECTIVE: Endometrium and cervical cancer is a common and important health problem that affects women in many physical, emotional and psychological aspects. This study aimed to determine the levels of depression and self-esteem in women with endometrial and cervical cancer receiving chemotherapy, determine the factors affecting them, and examine the relationship between the levels of depression and self-esteem. METHODS: This descriptive and cross-sectional study was conducted with 158 women who came to the gynecology-oncology policlinic and chemotherapy unit of a training and research hospital in Izmir, western Türkiye, between April 2022 and April 2023. Data were collected with the "Descriptive Information Form", "Beck Depression Inventory" and "Rosenberg Self-Esteem Scale". Descriptive and inferential statistics were performed to analyse the association between the study variables. RESULTS: In this study, 52.5% of women were diagnosed with endometrial cancer and 47.5% with cervical cancer. Beck Depression Inventory mean total score was 11.28 ±â€¯6.35, and 20.3% of them were at risk of depression (BDI ≥ 17). Rosenberg Self-Esteem Scale mean total score was 21.06 ±â€¯3.85, and 97.5% of them had high self-esteem. There was a statistically significant and strong negative correlation between the mean total scores of the Beck Depression Inventory and Rosenberg Self-Esteem Scale (r = 0.723; p < 0.05). It was determined that an increase in the Rosenberg Self-Esteem Scale mean total score by 1 unit decreased the Beck Depression Inventory mean total score by 1.2 units and was responsible for 52% of the variance (B = -1.192; R2 = 0.523). CONCLUSION: It was determined that one-fifth of women experienced moderate/severe depression and the majority of them had high self-esteem. The increase in women's depression levels decreased their self-esteem. Health professionals and oncology nurses should perform screenings to determine the depression and self-esteem levels of women with endometrial and cervical cancer and provide necessary education, counseling, and care to women.

Características clínicas en pacientes con menos de 12 folículos ováricos como hallazgo ecográfico / Clinical and ultrasound findings in patients with ovaries with a count of less than 12 follicles

Introducción y objetivos: Determinar los hallazgos clínicos y ecográficos en pacientes que presentan menos de 12 folículos ováricos. Método: Estudio observacional (cohorte histórica) con 505 pacientes seleccionadas mediante muestreo consecutivo, entre el 14 de enero del 2019 y el 15 de marzo del 2021, que consultan por diversas alteraciones ginecológicas. Se generan dos grupos de pacientes, las que presentaron uno a tres folículos en uno de los ovarios (n = 377) y las que presentaban 4 a 11 folículos (n = 128). Se midió como resultado primario la presencia de al menos un signo clínico de hiperandrogenismo. Resultados: De 505 pacientes analizadas, al comparar las que presentaron 4 a 11 folículos en uno de los ovarios (n = 377) con las que presentaban 1 a 3 folículos (n = 128), las primeras mostraron mayor presencia de signos de hiperandrogenismo, endometrio en fase lútea de mayor espesor y un patrón menstrual con uno a cuatro días de sangrado menstrual abundante, diferencias todas estadísticamente significativas (p < 0,05). Conclusión: En pacientes con 4 a 11 folículos en uno de sus ovarios, se observaron signos de hiperandrogenismo, similares al síndrome de ovario poliquístico.

Introduction and objectives: Determine the clinical and ultrasound findings in patients who present less than 12 ovarian follicles in the ultrasound count. Method: Observational study (historical cohort) with 505 patients selected by consecutive sampling, between January 14, 2019 and March 15, 2021, who consulted for different gynecological disorders. Two groups of patients were generated: those with 1 to 3 follicles in one of the ovaries (n = 377) and those with 4 to 11 follicles (n = 128). The primary outcome was the presence of at least one clinical sign of hyperandrogenism. Results: Of 505 patients analyzed, when comparing those who presented 4 to 11 follicles in one of the ovaries (n = 377) with those who presented 1 to 3 follicles (n = 128), the first group showed a greater presence of signs of hyperandrogenism, thicker endometrium in luteal phase and a menstrual pattern with one to four days of heavy menstrual bleeding, all differences were statistically significant (p < 0.05). Conclusion: In patients with 4 to 11 follicles in one of their ovaries, signs of hyperandrogenism, similar to polycystic ovary syndrome, were observed.

Prevalencia de endometritis crónica en mujeres infértiles establecida mediante histeroscopia y biopsia endometrial con CD138 / Prevalence of chronic endometritis in infertile women by hysteroscopy and endometrial biopsy with CD138

Resumen OBJETIVO: Determinar, mediante histeroscopia de evaluación y biopsia de endometrio, con análisis histológico endometrial e identificación de células plasmáticas con inmunohisdtoquímica con CD138 positiva, la prevalencia de endometritis crónica en pacientes infértiles. MATERIALES Y MÉTODOS: Estudio observacional, retrospectivo, efectuado de marzo de 2016 a noviembre del 2021 en el Centro de Reproducción Asistida de Saltillo (CREAS), Coahuila, México, en pacientes que consultaron por infertilidad. El diagnóstico de endometritis crónica se estableció mediante histeroscopia y biopsia de endometrio con inmunohistoquímica CD138. Se analizaron la prevalencia y precisión diagnóstica de la histeroscopia y la biopsia de endometrio. Además, la relación entre las características histeroscópicas específicas y la endometritis crónica confirmada por biopsia con CD138 positiva. RESULTADOS: La prevalencia de endometritis crónica por biopsia de endometrio CD138 positiva en las 170 pacientes estudiadas fue de 36% (n = 62) y por histeroscopia del 48.8% (n = 83), esta última con una sensibilidad del 48.3%, especificidad del 50.9%, valor predictivo positivo y negativo del 36.1 y 63.2%, respectivamente. En relación con las características histeroscópicas, la hiperemia endometrial tuvo una relación estadísticamente significativa con la prevalencia de endometritis crónica (p-value = 0.008; RM = 0.357; IC95%: 0.14-0.81) y con ≥ 2 características sugerentes de endometritis crónica (p-value = 0.015; RM = 3.63; IC95%: 1.15-12.69). CONCLUSIONES: En el procedimiento diagnóstico de la paciente infértil es importante descartar la endometritis crónica. Para ello es decisivo recurrir a herramientas diagnósticas, como la histeroscopia y confirmar el diagnóstico con una biopsia de endometrio con inmunohistoquímica CD138 positiva para que de esta manera pueda dirigirse el tratamiento.

Abstract OBJECTIVE: To determine the prevalence of chronic endometritis in infertile patients by evaluating hysteroscopy and endometrial biopsy with endometrial histologic analysis and identification of plasma cells by CD138-positive immunohistochemistry. MATERIALS AND METHODS: Observational, retrospective study performed from March 2016 to November 2021 at the Center for Assisted Reproduction of Saltillo (CREAS), Coahuila, Mexico, in patients who consulted for infertility. Chronic endometritis was diagnosed by hysteroscopy and endometrial biopsy with CD138 immunohistochemistry. The prevalence and diagnostic accuracy of hysteroscopy and endometrial biopsy were analysed. The association between specific hysteroscopic features and chronic endometritis confirmed by CD138-positive endometrial biopsy was also investigated. RESULTS: The prevalence of chronic endometritis by CD138-positive endometrial biopsy in the 170 patients studied was 36% (n = 62) and by hysteroscopy 48.8% (n = 83), the latter with a sensitivity of 48.3%, specificity of 50.9%, positive and negative predictive values of 36.1 and 63.2%, respectively. In relation to hysteroscopic features, endometrial hyperemia had a statistically significant relationship with the prevalence of chronic endometritis (p-value = 0.008; RM = 0.357; 95%CI: 0.14-0.81) and with ≥ 2 features suggestive of chronic endometritis (p-value = 0.015; RM = 3.63; 95%CI: 1.15-12.69). CONCLUSIONS: In the diagnostic process of infertile patients, it is important to exclude chronic endometritis. It is crucial to use diagnostic tools such as hysteroscopy and to confirm the diagnosis by endometrial biopsy with positive CD138 immunohistochemistry in order to guide treatment.

Netrina-1 en sangre como biomarcador para la detección del cáncer de endometrio / Serum Netrin-1 as a biomarker for Endometrium Cancer detection

RESUMEN Investigar la relación de la netrina-1 preoperatoria con factores clinicopatológicos y pronósticos importantes y los niveles de corte adecuados en pacientes con cáncer de endometrio. En este estudio prospectivo y observacional, el grupo de casos y el de controles se seleccionaron entre las pacientes que acudieron a la Clínica de Oncología Ginecológica. Se extrajeron 4 mL de sangre venosa en un tubo de bioquímica de cada paciente durante el período preoperatorio. Los valores de netrina para predecir la presencia de malignidad se analizaron mediante el análisis de la curva ROC (receiver operating characteristics). El valor de corte se calculó según el índice de Youden. En el estudio, el valor de corte de malignidad según el nivel de netrina fue determinado en 645,50 mg/dL en el análisis ROC (utilizando el índice de Youden). La probabilidad de malignidad en individuos con valores de netrina superiores a este punto de corte fue del 78,2% (IC 95%: 0,680 a 0,884). La sensibilidad de la netrina para mostrar la probabilidad de malignidad en este valor de corte fue del 87,5% y la especificidad del 63,6%. La netrina-1 puede ser un biomarcador potencial para la detección del cáncer de endometrio y la evaluación de su pronóstico.

ABSTRACT To investigate the relationship of preoperative netrin-1 with important clinicopathological and prognostic factors and appropriate cut-off levels in patients with endometrial cancer. In this prospective, observational study, the case and control group were selected among patients who applied to the Gynecological Oncology Clinic. Four mL of venous blood was drawn into a biochemistry tube from each patient during the preoperative period. Netrin values in predicting the presence of malignity were analyzed using ROC (receiver operating characteristics) curve analysis. The cut-off value was calculated according to the Youden index. In the study, the cut-off value of malignancy according to the netrin level was determined as 645.50 mg/dL in the ROC analysis (using the Youden index). The probability of malignancy in individuals with Netrin values above this cut-off was 78.2% (95% CI 0.680-0.884). The sensitivity of netrin in showing the probability of malignancy at this cut-off value was 87.5%, and the specificity 63.6%. Netrin-1 can be a potential biomarker for endometrial cancer detection and prognosis evaluation.

Clinical Characteristics and Outcomes of a High-grade Endometrial Cancer Cohort Treated at Instituto Nacional de Câncer, Brazil / Características clínicas e desfechos de uma coorte de câncer endometrial de alto grau tratada no Instituto Nacional de Câncer, Brasil

Abstract Objective To analyze the outcomes of a cohort of patients with high-risk histologies of endometrial cancer (EC) treated at Instituto Nacional de Câncer (National Cancer Institute, INCA, in Portuguese), in Brazil. Materials and Methods We reviewed the medical records of patients with high-risk histologies of EC in any stage registered at INCA between 2010 and 2016 to perform a clinical and demographic descriptive analysis and to evaluate the outcomes in terms of recurrence and survival. Results From 2010 to 2016, 2,145 EC patients were registered and treated at INCA, and 466 had high-grade histologies that met the inclusion criteria. The mean age of the patients was 65 years, 44.6% were Caucasian, and 90% had a performance status of 0 or 1. The most common histology was high-grade endometrioid (31.1%), followed by serous carcinoma (25.3%), mixed (20.0%), carcinosarcoma (13.5%), and clear cell carcinoma (9.4%). Considering the 2018 Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics, FIGO, in French) staging system, 44.8%, 12.4%, 29.8%, and 12.9% of the patient were in stages I, II, III or IV respectively. Age (> 60 years), more than 50% of myoinvasion, higher stage, poor performance status, serous and carcinosarcoma histologies, and adjuvant treatment were independent factors associated with recurrence-free survival (RFS) and overall survival (OS) in the multivariate analysis. Conclusion The current findings reinforced the international data showing poor outcomes of these tumors, especially for serous and carcinosarcomas and tumors with advanced stages, with shorter survival and high recurrence rates in distant sites, independently of the FIGO stage. Adjuvant therapy was associated with better survival.

Resumo Objetivo Analisar os desfechos de uma coorte de pacientes com câncer de endométrio (CE) e histologias de alto risco atendida no Instituto Nacional do Câncer (INCA) entre 2010 e 2016. Materiais e Métodos Foram revisados prontuários de pacientes com histologias de alto risco de CE em qualquer estágio cadastradas no INCA entre 2010 e 2016 para realizar uma análise descritiva clínica e demográfica e avaliar os resultados em termos de recorrência e sobrevida. Resultados De 2010 a 2016, 2.145 pacientes com CE foram cadastradas e atendidas no INCA, e 466 tinham histologias de alto grau e atendiam aos critérios de inclusão. A média de idade das pacientes foi de 65 anos, 44,6% eram brancas, e 90% tinham performance status de 0 ou 1. A histologia mais comum foi endometrioide de alto grau (31,1%), seguida de carcinoma seroso (25,3%), misto (20,0%), carcinossarcoma (13,5%) e carcinoma de células claras (9,4%). Considerando o estadiamento da Fédération Internationale de Gynécologie et d'Obstétrique (Federação Internacional de Ginecologia e Obstetrícia, FIGO, em francês) de 2018, 44,8%, 12,4%, 29,8% e 12,9% apresentaram estágios I, II, III ou IV, respectivamente. Idade (> 60 anos), mais de 50% de mioinvasão, estágio avançado, performance status ruim, histologias serosas e carcinossarcoma, e tratamento adjuvante foram fatores independentes associados à sobrevida livre de recorrência e sobrevida global na análise multivariada. Conclusão Os achados atuais reforçam os dados internacionais que demonstram o prognóstico ruim desses tumores, principalmente para as histologias serosas e carcinossarcomas e para estágios avançados, com menor sobrevida e altas taxas de recorrência à distância, independentemente do estágio da FIGO. A terapia adjuvante foi associada a melhor sobrevida.

Revisión sistemática sobre el papel de la 18F-FDG PET/TC preoperatoria para el pronóstico y la estratificación de riesgo en pacientes con cáncer de endometrio / A systematic review about the role of preoperative 18F-FDG PET/CT for prognosis and risk stratification in patients with endometrial cancer

objetivo Analizar la literatura disponible sobre el valor pronóstico de los parámetros metabólicos de la 18F-FDG PET/TC preoperatoria y su utilidad en la estratificación de riesgo en pacientes con cáncer de endometrio (CE). Material y métodos En búsquedas de Pubmed se utilizó «(endometr* OR uter*) AND (PET OR FDG)» como palabras clave desde enero-2000 hasta junio-2020. Se revisaron referencias en los artículos incluidos buscando posibles publicaciones no incluidas en la primera búsqueda. Se incluyeron los estudios que evaluaron el valor pronóstico de la 18F-FDG PET/TC preoperatoria y su papel para la estratificación del riesgo en pacientes con CE. Los artículos no originales (revisiones, editoriales, cartas, casos legales, entrevistas, informes de casos, etc.) no fueron incluidos. Resultados Veintiséis estudios (1.918 pacientes) fueron elegidos según los criterios de inclusión en esta revisión. Se incluyeron 13 estudios (939 pacientes) relacionados con el papel pronóstico de la 18F-FDG PET/TC preoperatoria y 14 estudios (1.036 pacientes) relacionados con su papel en la estratificación de riesgo. Parámetros como SUVmáx, volumen tumoral metabólico (VTM) y glicólisis total de lesión (GTL) del tumor primario fueron analizados. Conclusiones El SUVmáx preoperatorio es útil para realizar diagnósticos no invasivos y decidir la estrategia terapéutica adecuada, ya que podría utilizarse como marcador pronóstico independiente de recurrencia y supervivencia en el CE. Además, tanto VTM como GTL preoperatorios podrían ser factores pronósticos independientes para predecir recurrencia y supervivencia, pero, aun no existe suficiente evidencia científica. La utilidad del SUVmáx para la estratificación del riesgo es limitada (no existe literatura suficiente acerca de que la 18F-FDG PET/TC pueda sustituir la estadificación quirúrgica), aunque el VTM y la GTL sí que son más precisos y tienen un valioso papel en la estratificación del riesgo del CE (AU)

Objective To analyse the available literature on the prognostic value of preoperative 18F-FDG PET/CT metabolic parameters and their usefulness in risk stratification in patients with endometrial cancer (EC). Material and methods Pubmed searches used «(endometr* OR uter*) AND (PET OR FDG)» as keywords from January-2000 to June-2020. References in included articles were checked for possible publications not included in the first search. Studies evaluating the prognostic value of preoperative 18F-FDG PET/CT and its role for risk stratification in patients with EC were included. Non-original articles (reviews, editorials, letters, legal cases, interviews, case reports, etc.) were not included. Results Twenty-six studies (1918 patients) were selected according to the inclusion criteria in this review. Thirteen studies (939 patients) related to the prognostic role of preoperative 18F-FDG PET/CT and 14 studies (1036 patients) related to its role in risk stratification were included. Parameters such as SUVmax, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumour were analysed. Conclusions Preoperative SUVmax is useful for non-invasive diagnosis and for deciding the appropriate therapeutic strategy, as it could be used as an independent prognostic marker for recurrence and survival in EC. In addition, both preoperative VTM and GTL could be independent prognostic factors for predicting recurrence and survival, but there is still insufficient scientific evidence. The usefulness of SUVmax for risk stratification is limited (there is insufficient literature that 18F-FDG PET/CT can replace surgical staging), although VTM and GTL are more accurate and have a valuable role in risk stratification of EC. However, larger multicentre studies with adequate follow-up time are needed to confirm these findings (AU)

A systematic review about the role of preoperative 18F-FDG PET/CT for prognosis and risk stratification in patients with endometrial cancer.

OBJECTIVE: To analyse the available literature on the prognostic value of preoperative 18F-FDG PET/CT metabolic parameters and their usefulness in risk stratification in patients with endometrial cancer (EC). MATERIAL AND METHODS: Pubmed searches used "(endometr* OR uter*) AND (PET OR FDG)" as keywords from January-2000 to June-2020. References in included articles were checked for possible publications not included in the first search. Studies evaluating the prognostic value of preoperative 18F-FDG PET/CT and its role for risk stratification in patients with EC were included. Non-original articles (reviews, editorials, letters, legal cases, interviews, case reports, etc.) were not included. RESULTS: Twenty-six studies (1918 patients) were selected according to the inclusion criteria in this review. Thirteen studies (939 patients) related to the prognostic role of preoperative 18F-FDG PET/CT and 14 studies (1036 patients) related to its role in risk stratification were included. Parameters such as SUVmax, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumour were analysed. CONCLUSIONS: Preoperative SUVmax is useful for non-invasive diagnosis and for deciding the appropriate therapeutic strategy, as it could be used as an independent prognostic marker for recurrence and survival in EC. In addition, both preoperative VTM and GTL could be independent prognostic factors for predicting recurrence and survival, but there is still insufficient scientific evidence. The usefulness of SUVmax for risk stratification is limited (there is insufficient literature that 18F-FDG PET/CT can replace surgical staging), although VTM and GTL are more accurate and have a valuable role in risk stratification of EC. However, larger multicentre studies with adequate follow-up time are needed to confirm these findings.

Qualidade de vida e mapeamento de complicações: avaliação do linfonodo sentinela no câncer de endométrio / Quality of life and complications: evaluation of the sentinel lymph node in endometrial cancer

Objetivo: Avaliar a incidência das complicações pós-operatórias do estadiamento cirúrgico e qualidade de vida relacionada ao protocolo do linfonodo sentinela associado ou não à linfadenectomia sistemática no tratamento do câncer do endométrio. Métodos: Foi conduzida uma coorte prospectiva entre dezembro de 2017 e abril de 2022, incluindo mulheres com carcinoma de endométrio em estágio inicial presumido (doença restrita ao útero) e com estadiamento linfonodal, agrupadas em: Grupo LNS (somente pesquisa do linfonodo sentinela) e Grupo LNS+LND (linfonodo sentinela com adição de linfadenectomia sistemática). Foram incluídas pacientes com baixo e alto risco para metástase linfonodal. As pacientes de alto risco fazem parte do estudo ALICE (NCT03366051), um estudo prospectivo randomizado de não inferioridade. As pacientes foram avaliadas no pré-operatório, 1 mês, 6 e 12 meses, com aplicação de questionário de qualidade de vida (QQV) pelo EORTC QLQ-C30 e Cx24, avaliação clínica e perimetria para avaliar linfedema. Resultados: Foram incluídas 152 mulheres, sendo 113 (74,3%) no grupo LNS e 39 (25,7%) no grupo LNS+LND. Complicações cirúrgicas intraoperatórias ocorreram em 2 (1,3%) casos todas pertencentes ao grupo LNS+LND. Complicações cirúrgicas até 30 dias foram encontradas em 29 (19,1%) casos. As pacientes submetidas a LNS+LND apresentaram taxas gerais de complicações cirúrgicas mais altas em comparação com aquelas submetidas apenas a LNS (33,3% vs. 14,2%; p=0,011). O grupo LNS+LND apresentou maior tempo de cirurgia (p=0,001) e necessidade de UTI (p=0,001). A incidência de linfocele foi encontrada em 8 casos, apenas no grupo LNS+LND (0 vs. 20,5%; p<0,001). Para o linfedema de membros inferiores, não foi encontrada diferença entre os grupos pela avaliação perimétrica do grupo LNS comparado ao LNS+LND (23,2% vs. 13,3%; p= 0,25). O mesmo ocorreu para a avaliação clínica do linfedema, encontrado em 21,2% do grupo LNS e 33,3% do grupo LNS+LND (p=0,14). Entretanto, na avaliação de presença de linfedema pelo score de sintomas do EORTC, houve maior relato de linfedema no grupo LNS+LND (score 23,52) comparado ao grupo LNS (score 12,45) na avaliação de 12 meses (p=0,02). Além disso, encontramos associação entre avaliação clínica e linfedema relatado pelo paciente. O score médio de linfedema foi maior quando este foi detectado por exame clínico em 6 meses (30,10 vs. 7,8; p<0,001) e 12 meses (36,4 vs. 6,0; p<0,001), no entanto sem associação entre perimetria e avaliações clínicas (p=0,76). Em relação à avaliação global de qualidade de vida, não houve diferença entre os grupos aos 12 meses (p=0,21). Conclusões: Houve maior taxa geral de complicações para o grupo submetido a linfadenectomia sistemática, assim como maiores taxas de linfocele e linfedema pelo score de sintomas. Nenhuma diferença foi encontrada em relação à qualidade de vida entre os grupos LNS e LNS+LND

Objectives: To evaluate the incidence of postoperative complications of surgical lymph node staging procedures and quality of life related to the sentinel lymph node protocol associated or not with systemic lymphadenectomy in the treatment of endometrial cancer. Methods: A prospective cohort was conducted between December 2017 and April 2022. Women with presumed early-stage endometrial carcinoma (disease restricted to the uterus) and with lymph node staging were included, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND Group (sentinel lymph node with addition of systematic lymphadenectomy). Patients with low and high risk for lymph node metastasis were included, and high-risk patients were part of the ALICE study (NCT03366051), a prospective randomized non-inferiority study. The patients were assessed preoperatively, 1 month, 6 and 12 months with the application of a quality-of-life questionnaire (QQL) using the EORTC QLQ-C30 and Cx24, clinical evaluation and perimetry to assess lymphedema. Results: 152 women were included, 113 (74.3%) women in the SLN group and 39 (25.7%) in the SLN+LND group. Intraoperative surgical complications occurred in 2 (1.3%) cases, all of them in the SLN+LND group. Surgical complications within 30 days were found in 29 (19.1%) cases. Patients undergoing SLN+LND had higher overall rates of surgical complications compared to women undergoing SLN alone (33.3% vs. 14.2%; p=0.011). The SLN+LND group had longer surgery time (p=0.001) and need for ICU (p=0.001). The incidence of lymphocele was found in 8 cases and only in the SLN+LND group (0 vs. 20.5%; p<0.001). For lower limbs lymphedema, no difference was found between the groups by the perimetric evaluation of the SLN group compared to the SLN+LND (23.2% vs. 13.3%; p=0.25). The same occurred for the clinical evaluation of lymphedema, being found in 21.2% for the SLN group and 33.3% for the SLN+LND group (p=0.14). However, when evaluating the presence of lymphedema using the EORTC symptom score, there was a higher number of lymphedema reports in the SLN+LND group (score 23.52) compared to the SLN group (score 12.45) at the 12-month evaluation (p=0.02). In addition, we found an association between clinical evaluation and lymphedema reported by the patient. The lymphedema score had a higher mean score when lymphedema was detected by clinical examination at 6 months (30.10 vs. 7.8; p<0.001) and 12 months (36.4 vs. 6.0; p<0.001), however with no association between perimetry and clinical evaluations (p=0.76). Regarding the overall assessment of quality of life, there was no difference between the groups at 12 months (p=0.21). Conclusions: There was a higher overall rate of complications for the group undergoing systematic lymphadenectomy, as well as higher rates of lymphocele and lymphedema according to the symptom score. No difference was found regarding quality of life between the LNS and LNS+LND groups

Controversias en la técnica de detección del ganglio centinela en cáncer de endometrio / Controversy over sentinel lymph node detection in endometrial cancer

En la última década se ha introducido la biopsia selectiva del ganglio centinela en cáncer de endometrio de bajo riesgo, siendo opcional en el de riesgo intermedio y alto. Sin embargo, hasta hace un año no se existía consenso respecto al grupo de población indicado, el trazador de elección o el lugar de administración del trazador. En este trabajo, presentamos de forma multidisciplinar los aspectos más controvertidos sobre la técnica de detección del ganglio centinela en cáncer de endometrio, con mayor énfasis en las ventajas y desventajas de los tipos de trazadores disponibles: radiotrazadores, trazadores híbridos y verde de indocianina (AU)

In the last decade, the procedure of sentinel lymph node biopsy has been introduced in low-risk endometrial cancer, being optional in intermediate- and high-risk cancer. However, until the last year, there was no consensus regarding the group of patients to whom to apply it, the best tracer to use or the site of injection. In this paper, we present in a multidisciplinary view the most controversial issues about the sentinel lymph node procedure in endometrial cancer, emphasizing the pros and cons of the different tracers available: radiotracers, hybrid tracers and indocyanine green (AU)

Cirugía laparoscópica en pacientes con obesidad mórbida y cáncer de endometrio

Introducción: La cirugía, en pacientes con obesidad mórbida, como tratamiento del cáncer ginecológico supone un reto para el cirujano y el anestesiólogo, pues se asocia a un incremento de las complicaciones intra y posoperatorias. Objetivo: Describir los principales resultados con la cirugía laparoscópica, en pacientes con obesidad mórbida y adenocarcinoma de endometrio, tratadas en el Instituto Nacional de Oncología y Radiobiología (INOR) de la Habana, Cuba, en el período comprendido enero de 2019 a marzo de 2020. Método: Se realizó un estudio descriptivo, observacional y transversal, en 22 pacientes con índice de masa corporal mayor de 40 kg/m2 y diagnóstico de adenocarcinoma de endometrio, que fueron sometidas a cirugía laparoscópica. El dato primario fue obtenido a través de las historias clínicas, con los que se confeccionó una base de datos en una hoja de Microsoft Excel para sintetizar toda la información. Resultados: Predominó la edad entre 61 a 70 años. El adenocarcinoma endometrioide fue el más frecuente con el 77,27 %. El grado de diferenciación fue el bien diferenciado, infiltrando menos del 50 % del miometrio. El estadiamiento quirúrgico predominante fue el IA (72,72 %). El sangrado transoperatorio fue de 78,9 ± 5,7ml (rango 10 y 200 ml), la media del acto operatorio de 82 min (rango 75-132 min), y la estadía hospitalaria de menos de 24 horas (90,90 %). La conversión quirúrgica se realizó en el 4,54 % de los casos. Conclusiones: Las pacientes con obesidad mórbida pueden beneficiarse del abordaje laparoscópico para el tratamiento y la estatificación quirúrgica laparoscópica del carcinoma endometrial, lo que disminuye la morbilidad y la estadía hospitalaria.

Introduction: Surgery in morbidly obese patients as a treatment for gynecologic cancer is a challenge for surgeons and anesthesiologists, since it is associated with the processes of increasing intraoperative and postoperative complications. Objective: To describe the main results gained with the use of laparoscopic surgery in patients with morbid obesity and endometrial adenocarcinoma treated at the Instituto Nacional de Oncología y Radiobiología (INOR) of Havana, Cuba, from January 2019 to March 2020. Method: A descriptive, observational, cross-sectional study was carried out in 22 patients, with body mass index more than 40 kg/m2 and diagnosis of endometrial adenocarcinoma, who underwent laparoscopic surgery. The primary data was obtained from the medical records, which were used to create a database in a Microsoft Excel spreadsheet to synthesize all the information. Results: The predominant age group was between 61 and 70 years old. Endometrial adenocarcinoma was the most frequent cancer (77.27%). The degree of differentiation was well differentiated, infiltrating less than 50 % of the myometrium. The predominant surgical staging was IA (72.72%). Transoperative bleeding was 78.9 ± 5.7 ml (range between 10 and 200 ml), mean operative time was 82 min (range 75-132 min), and hospital stay was less than 24 hours (90.90%). Surgical conversion was performed in 4.54% of cases. Conclusions: Morbidly obese patients may benefit from the laparoscopic approach for the treatment and laparoscopic surgical staging of endometrial carcinoma, which decreases morbidity and hospital stay.

Introdução: A cirurgia, em pacientes com obesidade mórbida, como tratamento para o câncer ginecológico é um desafio para o cirurgião e para o anestesiologista, pois está associada ao aumento de complicações intra e pós-operatórias. Objetivo: Descrever os principais resultados da cirurgia laparoscópica, em pacientes com obesidade mórbida e adenocarcinoma endometrial, tratados no Instituto Nacional de Oncología y Radiobiología (INOR) em Havana, Cuba, no período de janeiro de 2019 a março de 2020. Método: A estudo descritivo, observacional e transversal realizado em 22 pacientes com índice de massa corporal superior a 40 kg/m2 e diagnóstico de adenocarcinoma de endométrio, submetidas à cirurgia laparoscópica. Os dados primários foram obtidos por meio dos prontuários, com os quais foi criado um banco de dados em uma planilha do Microsoft Excel para sintetizar todas as informações. Resultados: Predominou a idade entre 61 a 70 anos. O adenocarcinoma endometrioide foi o mais frequente com 77,27%. O grau de diferenciação foi bem diferenciado, infiltrando menos de 50% do miométrio. O estadiamento cirúrgico predominante foi IA (72,72%). O sangramento transoperatório foi de 78,9 ± 5,7 ml (variação de 10 e 200 ml), a média do ato cirúrgico foi de 82 min (variação de 75-132 min) e o tempo de internação foi inferior a 24 horas (90,90%). A conversão cirúrgica foi realizada em 4,54% dos casos. Conclusões: Pacientes com obesidade mórbida podem se beneficiar da abordagem laparoscópica para o tratamento e estadiamento cirúrgico laparoscópico do carcinoma endometrial, o que diminui a morbidade e o tempo de internação.

Metástasis de carcinoma medular de tiroides en endometrio: reporte de un caso y revisión de la literatura / Metastasis of medullary thyroid carcinoma to the endometrium: A case report and review of the literature

Las metástasis uterinas de tumores extrapélvicos son raras y, cuando el útero se ve involucrado, es usualmente por extensión directa de neoplasias de órganos adyacentes. Se presenta el caso de una mujer de 68 años con antecedente de tiroidectomía total, que concurrió con incontinencia urinaria asociada a episodios de metrorragia. Se le realizó un legrado debido a un engrosamiento endometrial y se reconoció una proliferación de células neoplásicas con núcleos ovales, cromatina en «sal y pimienta», nucléolos evidentes y moderada cantidad de citoplasma eosinófilo, las cuales resultaron positivas con CKAE1/AE3, TTF-1, CEA y calcitonina. Los hallazgos histológicos e inmunohistoquímicos correspondieron a una metástasis de un carcinoma medular de tiroides.Si bien las metástasis en el útero son extremadamente infrecuentes, el sangrado uterino anormal podría ser la única expresión clínica y se debería pensar en ello cuando los antecedentes de la paciente y los hallazgos histológicos no sean característicos de una lesión primaria.(AU)

Uterine metastases from extra pelvic tumors are rare; involvement of the uterus is usually by direct neoplastic extension from adjacent organs. We report the case of a 68-year-old woman with a history of total thyroidectomy. She presented with urinary incontinence associated with episodes of metrorrhagia. Ultrasound showed a thickened endometrium. A legrado was performed and the biopsy revealed a proliferation of neoplastic cells with oval nuclei, «salt and pepper» chromatin, evident nucleoli and a moderate amount of eosinophilic cytoplasm. These cells were positive for CKAE1 / AE3, TTF-1, CEA and calcitonin. The histological and immunohistochemical findings corresponded to a metástasis from a medullary thyroid carcinoma. Although metastatic tumors in the uterus are extremely rare, they may give rise to abnormal uterine bleeding and should be considered when the patient's history and the histological findings are not characteristic of a primary lesion.(AU)

Controversy over sentinel lymph node detection in endometrial cancer.

In the last decade, the procedure of sentinel lymph node biopsy has been introduced in low-risk endometrial cancer, being optional in intermediate- and high-risk cancer. However, until the last year, there was no consensus regarding the group of patients to whom to apply it, the best tracer to use or the site of injection. In this paper, we present in a multidisciplinary view the most controversial issues about the sentinel lymph node procedure in endometrial cancer, emphasizing the pros and cons of the different tracers available: radiotracers, hybrid tracers and indocyanine green.

[Familial endometrial adenocarcinoma: MSH6 variant of unknown significance in the presence of phenocopy, what should be done?] / Adenocarcinoma de endometrio en una familia: variante de significado incierto en MSH6 en presencia de fenocopia, ¿cómo resolverlo?

Endometrial cancer (EC) is the second most common tumor in women with Lynch syndrome, and can be its first manifestation. It may exhibit negative immunostaining for DNA mismatch-repair proteins and/or microsatellite instability. We present the case of a woman with EC in which a MSH6 variant of unknown significance was identified. To establish the pathogenicity of the variant, the family study was extended, identifying her healthy sister as a carrier while her aunt, with EC, was not. In the latter, the histopathology of a first tumor block did not identify the pathway of carcinogenesis, but its repetition in a second tumor block suggested the possibility of it being a phenocopy. The multidisciplinary approach in the study of this family allowed a correct diagnosis of the different adenocarcinomas, adequate family genetic counselling and the correct assignment of pathogenicity to a variant in MSH6.

[Metastasis of medullary thyroid carcinoma to the endometrium: A case report and review of the literature]. / Metástasis de carcinoma medular de tiroides en endometrio: reporte de un caso y revisión de la literatura.

Uterine metastases from extra pelvic tumors are rare; involvement of the uterus is usually by direct neoplastic extension from adjacent organs. We report the case of a 68-year-old woman with a history of total thyroidectomy. She presented with urinary incontinence associated with episodes of metrorrhagia. Ultrasound showed a thickened endometrium. A legrado was performed and the biopsy revealed a proliferation of neoplastic cells with oval nuclei, «salt and pepper¼ chromatin, evident nucleoli and a moderate amount of eosinophilic cytoplasm. These cells were positive for CKAE1 / AE3, TTF-1, CEA and calcitonin. The histological and immunohistochemical findings corresponded to a metástasis from a medullary thyroid carcinoma. Although metastatic tumors in the uterus are extremely rare, they may give rise to abnormal uterine bleeding and should be considered when the patient's history and the histological findings are not characteristic of a primary lesion.

Sentinel Lymph Node Biopsy in Endometrial Cancer - A Systematic Review and Quality Assessment of Meta-Analyses / Biópsia do linfonodo sentinela no câncer de endométrio - Uma revisão sistemática e avaliação da qualidade de meta-análises

Abstract Objective To assess the quality of recent meta-analyses reviewing the diagnostic utility of sentinel node biopsy in endometrial cancer. Methods With the MeSH terms endometrial neoplasms and sentinel lymph node biopsy, PubMed and Embase databases were searched on October 21, 2020, and again on November 10, 2021, with meta-analysis and publication date filters set to since 2015. The articles included were classified with the A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) assessment tool. Results The database searches found 17, 7 of which, after the screening, were selected for full review by the author, finally extracting six meta-analyzes for quality analysis. The rating with the AMSTAR 2 assessment tool found that overall confidence in their results was critically low. Conclusion This study found that the quality of recent meta-analyses on the utility of the staging of endometrial cancer with sentinel node biopsy, evaluated by the AMSTAR 2 assessment tool, is classified as critically low, and, therefore, these meta-analyses are not reliable in the summary of their studies.

Resumo Objetivo Avaliar a qualidade de meta-análises recentes que revisaram a utilidade diagnóstica da biópsia do linfonodo sentinela no câncer de endométrio. Métodos Com os termos MeSH endometrial neoplasms e =biópsia do linfonodo sentinela, as bases de dados PubMed e Embase foram pesquisadas em 21 de outubro de 2020 e novamente em 10 de novembro de 2021, com filtros de meta-análise e data de publicação configurados para desde 2015. Os artigos incluídos foram classificados com o instrumento de avaliação A Measurement Tool to Assess Systematic Reviews (AMSTAR 2). Resultados As pesquisas de banco de dados encontraram 17 artigos, sete dos quais, após a triagem, foram selecionados para revisão completa pelo autor, extraindo finalmente 6 meta-análises para análise de qualidade. A classificação com a ferramenta de avaliação AMSTAR 2 descobriu que a confiança geral em seus resultados era criticamente baixa. Conclusão Este estudo constatou que a qualidade de meta-análises recentes sobre a utilidade do estadiamento do câncer de endométrio com biópsia do linfonodo sentinela, avaliada pela ferramenta de avaliação AMSTAR 2, é classificada como criticamente baixa e, portanto, essas meta-análises não são confiáveis no resumo de seus estudos.

Tumor carcinoide de células caliciformes apendicular con metástasis endometrial

El tumor carcinoide de células caliciformes es una neoplasia mixta casi exclusiva del apéndice, con diferenciación neuroendocrina y mucinosa. La afección metastásica endometrial por carcinomas extragenitales, especialmente el tipo de células de anillo de sello, es rara. Se presenta un caso de tumor carcinoide de células caliciformes apendicular con metástasis endometrial. Se trató de paciente femenina de 70 años quien presentó sangrado genital. El examen ginecológico mostró sangrado genital en moderada cantidad de color rojo-marrón y cuello uterino endurecido. En la biopsia endometrial se halló nidos de células de anillo de sello. La impresión diagnóstica provisional fue carcinoma mal diferenciado de probable origen intestinal. Durante la intervención, el útero tenía consistencia pétrea, el apéndice cecal era fibrótico y engrosado y el epiplón engrosado con nódulos tumorales. Las secciones anatómicas del cuello y cuerpo uterino mostraron focos tumorales. En el apéndice cecal se encontró acúmulos de pequeño tamaño compuestos por células caliciformes. La inmunotinción fue positiva a sinaptofisina, CDX-2, EMA, CK20, CD56 focal. Estos hallazgos confirmaron el diagnóstico de tumor carcinoide de células caliciformes, un tumor caracterizado por infiltración de la pared apendicular por pequeños nidos o cordones de células caliciformes con mucina intracitoplasmática y expresión focal de marcadores neuroendocrinos. Estas neoplasias tienen un comportamiento más agresivo que los tumores neuroendocrinos. La metástasis endometrial es rara y puede ser confundida con un carcinoma primario de células de anillo de sello. Se debe considerar como diagnóstico diferencial después de excluir otros tumores primarios.

Goblet cell carcinoid tumor is an almost exclusive mixed neoplasm of the appendix with neuroendocrine and mucinous differentiation. Endometrial metastatic involvement by extragenital carcinomas, especially the signet ring cell type, is rare. A case of appendiceal goblet cell carcinoid tumor with endometrial metastasis is presented. This was a 70-year-old female patient who presented with genital bleeding. The gynecological examination showed moderate red-brown genital bleeding and hardened cervix. Endometrial biopsy reported nests of signet ring cells. The provisional diagnostic impression was poorly differentiated carcinoma of probable intestinal origin. During surgery, the uterus had a stony consistency, the cecal appendix was fibrotic and thickened, and the omentum was thickened with tumor nodules. Anatomical sections of the cervix and uterine body showed tumor foci. In the cecal appendix, small clusters composed of goblet cells were found. Immunostaining was positive for synaptophysin, CDX-2, EMA, CK20, focal CD56. These findings confirmed the diagnosis of goblet cell carcinoid tumor, a tumor characterized by infiltration of the appendiceal wall by small nests or cords of goblet cells with intracytoplasmic mucin and focal expression of neuroendocrine markers. These neoplasms have a more aggressive behavior than neuroendocrine tumors. Endometrial metastasis is rare and can be mistaken for a primary signet ring cell carcinoma. It should be considered as a differential diagnosis after other primary tumors have been excluded.

Effect of autologous platelet-rich plasma treatment on patients with thin endometrium / Efecto del tratamiento con plasma autólogo rico en plaquetas en pacientes con endometrio delgado

ABSTRACT Introduction: The success of frozen embryo transfer cycles depends on a delicate interaction between embryo quality and endometrium. Low pregnancy rates are associated with a thin endometrium. Objective: To evaluate the effect of autologous platelet-rich plasma treatment on patients with thin endometrium. Methods: In 34 patients with thin endometrium (< 7 mm), canceled in the previous frozen embryo transfer cycles, autologous platelet-rich plasma was prepared, from autologous peripheral vein blood; intrauterine infusion was given during hormone replacement therapy in frozen embryo transfer cycles. Frozen embryo transfer was performed when the endometrium thickness reached ≥ 7mm. Results: Six patients canceled the embryo transfer cycle due to endometrium thickness did not reach 7 mm; 28 patients got endometrial thickness ≥ 7 mm and performed frozen embryo transfer. The endometrial thickness was 7.5 ± 0.8 mm, which was significantly thicker than in the previous cycles (5.6 ± 0.79 mm) with p< 0.002, the implantation rate was 23.07 %, and the clinical pregnancy rate was 12/28 (42.8 %). Conclusion: Autologous platelet-rich plasma improves the endometrial thickness and the pregnancy rate outcomes in women with thin endometrium.

RESUMEN Introducción: El éxito de los ciclos de transferencia de embriones congelados depende de una delicada interacción entre la calidad del embrión y el endometrio. Las bajas tasas de embarazo están asociadas con un endometrio delgado. Objetivo: Evaluar el efecto del tratamiento con plasma rico en plaquetas autólogo en pacientes con endometrial delgado. Métodos: En 34 pacientes con endometrio delgado (< 7 mm) canceladas en los ciclos previos de transferencia de embriones congelados, se preparó plasma autólogo rico en plaquetas, a partir de sangre autóloga de venas periféricas; la infusión intrauterina se administró durante la terapia de reemplazo hormonal en los ciclos de transferencia de embriones congelados. La transferencia de embriones congelados se realizó cuando el grosor del endometrio alcanzó ≥ 7 mm. Resultados: En 6s pacientes se canceló el ciclo de transferencia embrionaria debido a que el grosor del endometrio no alcanzó los 7 mm; 28 pacientes obtuvieron un grosor endometrial ≥ 7 mm y realizaron transferencia de embriones congelados. El grosor del endometrio fue de 7,5 ± 0,8 mm, significativamente mayor que en los ciclos anteriores (5,6 ± 0,79 mm) con p< 0,002; la tasa de implantación fue de 23,07 % y la tasa de embarazo clínico fue de 12/28 (42,8 %). Conclusión: El plasma autólogo rico en plaquetas mejora el grosor endometrial y los resultados de la tasa de embarazo en mujeres con endometrio delgado.

Protein biomarkers in gynecological cancers: The need for translational research towards clinical applications / Biomarcadores proteicos en los cánceres ginecológicos: la necesidad de una investigación traslacional para las aplicaciones clínicas

Ovarian cancer is ranked highest among gynecological cancers, followed by cervical and endometrial cancer. Most women are asymptomatic and are eventually diagnosed with late-stage disease. Numerous recent studies have proposed promising protein tumour biomarkers for diagnosis, prognosis, treatment and disease recurrence. Cancer antigen 125 (CA-125) and human epididymis protein 4 (HE4) are biomarkers routinely used for monitoring recurrence in ovarian cancer patients. They are of limited diagnostic value in early-stage cancer. Application of sensitive advanced proteomics techniques reveals that a combined biomarker panel is superior in specificity and sensitivity compared to a single biomarker. The major limitation in translating potential tumour biomarkers from the research setting to clinical practice is a lack of validation in large patient cohorts. This review provides an overview of current and potential biomarkers for ovarian, endometrial and cervical cancers. In conclusion, we propose validation studies for multiple biomarker panels of apolipoprotein A-I (ApoA-I)+CA-125+transthyretin and vascular cell adhesion molecule-1 (VCAM-1)+CA-125+carcinoembryonic antigen (CEA)+HE4 for early diagnosis of ovarian cancer. We also suggest combination panels of prognostic value consisting of CA-125+HE4 for endometrial cancer and squamous cell carcinoma antigen (SCC-Ag)+CEA for cervical cancer.

El cáncer de ovario ocupa el primer lugar entre los cánceres ginecológicos, seguido del cáncer de cuello uterino y del cáncer de endometrio. La mayoría de las mujeres son asintomáticas, por lo que finalmente se les diagnostica la enfermedad en una fase avanzada. En numerosos estudios recientes se han propuesto prometedores biomarcadores tumorales proteicos para el diagnóstico, el pronóstico, el tratamiento y la recidiva de la enfermedad. El antígeno de cáncer 125 (CA-125) y la proteína 4 del epidídimo humano son biomarcadores que se utilizan de forma habitual para controlar la recidiva en pacientes con cáncer de ovario. Tienen un valor diagnóstico limitado en las fases iniciales del cáncer. La aplicación de técnicas sensibles de proteómica avanzada ha revelado que un grupo combinado de biomarcadores es superior en especificidad y sensibilidad en comparación con un único biomarcador. La principal limitación a la hora de trasladar los posibles biomarcadores tumorales del ámbito de la investigación a la práctica clínica es la falta de validación en grandes cohortes de pacientes. Esta revisión ofrece una visión general de los biomarcadores actuales y potenciales para el cáncer de ovario, de endometrio y de cuello uterino. En conclusión, proponemos estudios de validación para varios grupos de biomarcadores de apolipoproteína A-I+CA-125+transtiretina y molécula de adhesión celular vascular 1+CA-125+antígeno carcinoembrionario+proteína 4 del epidídimo humano para el diagnóstico precoz del cáncer de ovario. También sugerimos grupos combinados de valor pronóstico, compuestos por CA-125+proteína 4 del epidídimo humano para el cáncer de endometrio y antígeno de carcinoma de células escamosas+ antígeno carcinoembrionario para el cáncer de cuello uterino.

Manejo terapéutico del cáncer ginecológico durante la gestación / Therapeutic management of gynecological cancer during pregnancy

Antecedente: Aunque la asociación entre embarazo y cáncer es infrecuente, el retraso en la edad de gestación ha hecho que aumente la incidencia en las últimas décadas. El tratamiento del cáncer gine- cológico durante la gestación plantea un importante conflicto tanto a nivel ético como clínico. Objetivo: Material y métodos: Búsqueda bibliográfica de literatura a través de las bases de datos Pub- Med, MedLine, Embase, BioMed Central y SciELO.Conclusiones: La gestación no ha demostrado tener un impacto negativo en el pronóstico del cáncer de cérvix. La cirugía más o menos radical en función de la sospecha de malignidad es el manejo estándar del cáncer de ovario en el embarazo, aunque resultan prometedores los resultados de las pautas neoad- yuvantes con platino. El embarazo actúa como factor protector de cáncer de endometrio. (AU)

Background: Although the association between pregnancy and cancer is rare, the delay in gestation age has increased theincident in recent decades. The treatment of gynecological cancer during pregnancy involves an important conflict bothan ethical and clinical level.Objetive: To collect the current evidence regarding the diagnosis and management of gynecological cancer during preg-nancy.Material and methods: Bibliographic literature search through the Pubmed, MedLine, Embase, BioMed Central andSciELO databases.Conclusions: Pregnancy has not been shown to have a negative impact on the prognosis of cervical cancer. More or lessradical surgery based on suspected malignancy is the standard management of ovarian cancer in pregnancy, although theresults of neoadjuvant platinum regimens are promising. Pregnancy acts as a protective factor against endometrial cancer. (AU)

Estudo imuno-histoquímico e classificação molecular dos adenocarcinomas de endométrio com expressão heterogênea dos genes de reparo do DNA / Immunohistochemical study and molecular classification of endometrial adenocarcinomas with heterogeneous expression of DNA repair genes

Introdução: O carcinoma endometrial (CE) foi classificado pelo sistema de Bokhman em tipos I e II com base em observações clínicas e epidemiológicas. O tipo I corresponde aos tumores de baixo grau e o tipo II aos tumores de alto grau. Adicionalmente, estudos recentes propuseram que a classificação também fosse baseada em aspectos histológicos e moleculares com base nos dados do TCGA (The Cancer Genome Atlas). Foram identificados quatro grupos moleculares distintos de CE: (1) com mutações no POLE (fenótipo "ultramutado"), (2) "alto número de cópias" (mutações em TP53), (3) !baixo número de cópias" (em que os tumores não apresentam nenhuma das alterações descritas nos outros tipos) e (4) tumores com predomínio de instabilidade de microssatélites. A imunohistoquímica (IHC) para proteínas do gene de reparo é usada para identificar a deficiência de genes de reparo do DNA (Mismatch Repair ­ MMR) associada à instabilidade de microssatélites(MSI). A coloração nuclear positiva representa a expressão retida de proteínas MMR, enquanto a perda completa representa deficiência de MMR. O padrão de expressão heterogênea (HEP), ou seja, concomitância em um mesmo espécime de áreas positivas e totalmente negativas tem sido observada em CE. No presente momento, as principais diretrizes determinam que a presença de HEP seja interpretada como expressão retida de proteínas MMR. Não há, porém, consenso quanto à classificação e interpretação de HEP, nem conhecimento do impacto da classificação de HEP como subtipo molecular diferente em relação às características clínicas e prognósticas. Objetivos: realizar a classificação molecular dos casos de CE com HEP das proteínas relacionadas aos genes de reparo do DNA e comparação do perfil molecular entre áreas positivas e negativas no estudo imunohistoquímico. Materiais e Métodos: De janeiro/2007 a dezembro/2017 foram identificados 356 casos de CE, 16 deles com HEP. A classificação molecular foi feita com base no protocolo PROMISE para CE. Cada área (expressão retida ou perdida) foi macrodissecada e o status molecular foi avaliado separadamente quanto ao status MSI (Idylla), metilação do promotor MLH1 (NGS - ponto de corte para positividade ≥ 15%), status POLE (NGS) e status p53 (IHC). Variáveis clínicas e patológicas também foram avaliadas e correlacionadas com cada caso. Resultados: A histologia endometrioide foi predominante (15 casos), bem como ausência de invasão linfovascular (11 casos), ausência de padrão MELF (10 casos), graus FIGO 1 e 2 (13 casos), invasão miometrial < 50% (13 casos) e estadiamento T1 (13 casos). Todos os pacientes estavam vivos e sem evidência de doença no último acompanhamento, exceto por um caso, cujo status de sobrevida era desconhecido. Dois casos que seriam descritos como apresentando expressão retida de proteínas relacionadas a genes de reparo do DNA por IHC apresentaram-se na análise molecular com instabilidade de microssatélites(MSI-H). Nos casos de HEP, a proteína MSH6 foi a maisfrequentemente envolvida (9 casos, 7 isolados). A proteína MLH1 apresentou-se alterada em 6 casos, sendo a única proteína associada a co-alterações (com MSH6 e PMS2). Seis casos apresentaram-se metilados por MLH1, padrão encontrado tanto em áreas com perda quanto em áreas com retenção das proteínas relacionadas a MMR por IHC e dois casos apresentaram metilação em apenas uma das áreas. Em relação ao status de POLE, 6 casos apresentaram mutação, 2 com mutações tanto em áreas com perda quanto em áreas com retenção de expressão, 3 apenas na área com perda e 1 apenas na área com retenção. Dois casos apresentam padrão aberrante de p53 (MSH6 alterados) em ambas as áreas. Conclusão: em pacientes portadoras CE e com tumores apresentando HEP a correlação entre a IHC e os achados moleculares é heterogênea e o diagnóstico entre casos com retenção ou das proteínas relacionadas a MMR não é factível apenas com realização de IHC. A análise molecular deve ser realizada em todos os casos de CE com HEP para determinar adequadamente as característicasintrínsecas de cada tumor. Devido à raridade desse achado, esta proposta é financeiramente viável e tem o potencial de mudar a prática clínica em um subconjunto de pacientes, permitindo tratamentos inovadores. HEP deve ser relatado como um padrão distinto e não considerado como uma expressão sinônimo de expressão retida de proteínas MMR em CE.

Introduction: Endometrial adenocarcinoma is classified by the Bokhman system in type I and II based on clinical and epidemiological observations, whereas the type I represents low grade tumors and type II high grade tumors. Additionally, a classification based on histological aspects and molecular profile has been proposed. The TCGA (The Cancer Genome Atlas) identified four molecular groups of endometrial adenocarcinomas: (1) mutations in POLE ("ultramutated" phenotype), (2) "high copy number" (mutations in TP53), (3) "low number of copies " (in which the tumors do not exhibit any of the changes described in the other types) and (4) tumors with predominance of microsatellite instability. In a small number of patients, heterogeneous staining is observed in the evaluation protein expression for mismatch repair genes. Objectives: to evaluate and perform the molecular classifications of cases of endometrial carcinoma with heterogeneous staining by IHC of proteins related to mismatch repair genes and comparison of the molecular profile of positive and negative areas in the IHC study. Cases and Methods: From January/2007 to December/2017 354 cases with EC were identified, 16 of those with HEP. Molecular classification was made based on the PROMISE protocol for EC. Each area (retained and lost expression) was macrodissected and molecular status was evaluated separately regarding MSI status (Idylla), MLH1 promoter methylation (NGS - cutoff for positivity ≥ 15%), POLE status (NGS) and p53 status (IHC). Clinical and pathologic variables were also evaluated and correlated with each case. Results: Endometrioid histology was predominant (15 cases), as absent lymphovascular invasion (11 cases), absence of MELF pattern (10 cases), FIGO Grade 1 and 2 (13 cases), and T1 stage (13 cases). All patients were alive and disease-free at the last follow-up. Two cases that would be described as retained by IHC presented in the molecular analysis as MSI-H. In HEP cases MSH6 was more frequent (9 cases, 7 isolated). MLH1 was altered in 6 cases, and wasthe only protein associated with co-alterations (with MSH6 and PMS2). Six cases were MLH1 methylated, found both in lost and retained areas. As POLE status, there were 6 mutated cases, 2 of those with mutations both in lost and retained areas, and 3 the lost area. Two cases had p53 aberrant pattern (MSH6 altered), that was seen both in the retained and in the lost areas. Conclusion: Correlation between IHC and molecular findings is heterogeneous, and determination between retained or lost expression of MMR proteins by IHC when HEP occurs, however feasible, does not represent the actual molecular alterations. Thus, molecular analysis should be performed every case to adequately determine the intrinsic features of each tumor. Due to the rarity of this finding, this is financially viable and has the potential to change clinical practice in a subset of patients. HEP should be reported as a distinct pattern, and not considered as a synonym expression of retained expression of MMR proteins in EC.