Diagnosis of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology / 中华神经科杂志

Endometrial carcinoma is one of common malignant tumors in female reproductive system, but it is extremely rare in leptomeningeal metastasis. The clinical manifestations and signs of meningeal carcinomatosis are complex and not specific. It is difficult to get a precise diagnosis early, and it has high rate of misdiagnosis and missed diagnosis. Accurate diagnosis and treatment of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology are reported. The patient is an elderly female with a history of endometrial cancer. The main manifestations were fever, headache and dizziness; cerebrospinal fluid cytology showed tumor cells; AKT1 gene and TP53 gene were detected in endometrial carcinoma tissue, plasma and cerebrospinal fluid by next-generation sequencing. After treatment with intrathecal chemotherapy, immunotherapy combined with anti angiogenesis, the patient′s condition still progressed gradually and died finally. The purpose of this case report is to raise clinical awareness of recognition and treatment in early meningeal metastasis of endometrial carcinoma.

Uterine POLE mutant endometrioid carcinoma combined with human papilloma virus-associated cervical adenocarcinoma: A case report and literature review / 北京大学学报(医学版)

Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.

Endometrioid adenocarcinoma with proliferated stromal cells, hyalinization and cord-like formations: A case report / 北京大学学报(医学版)

Corded and hyalinized endometrioid carcinoma (CHEC) is a morphologic variant of endo-metrioid adenocarcinoma. The tumor exhibits a biphasic appearance with areas of traditional low-grade adenocarcinoma merging directly with areas of diffuse growth composed of epithelioid or spindled tumor cells forming cords, small clusters, or dispersed single cells. It is crucial to distinguish CHEC from its morphological mimics, such as malignant mixed mullerian tumor (MMMT), because CHECs are usually low stage, and are associated with a good post-hysterectomy prognosis in most cases while the latter portends a poor prognosis. The patient reported in this article was a 54-year-old woman who presented with postmenopausal vaginal bleeding for 2 months. The ultrasound image showed a thickened uneven echo endometrium of approximately 12.2 mm and a detectable blood flow signal. Magnetic resonance imaging revealed an abnormal endometrial signal, considered endometrial carcinoma (Stage Ⅰ B). On hysterectomy specimen, there was an exophytic mass in the uterine cavity with myometrium infiltrating. Microscopically, most component of the tumor was well to moderately differentiated endometrioid carcinoma. Some oval and spindle stromal cells proliferated on the superficial surface of the tumor with a bundle or sheet like growth pattern. In the endometrial curettage specimen, the proliferation of these stromal cells was more obvious, and some of the surrounding stroma was hyalinized and chondromyxoid, which made the stromal cells form a cord-like arrangement. Immunostains were done and both the endometrioid carcinoma and the proliferating stroma cells showed loss of expression of DNA mismatch repair protein MLH1/PMS2 and wild-type p53 protein. Molecular testing demonstrated that this patient had a microsatellite unstable (MSI) endometrial carcinoma. The patient was followed up for 6 months, and there was no recurrence. We diagnosed this case as CHEC, a variant of endometrioid carcinoma, although this case did not show specific β-catenin nuclear expression that was reported in previous researches. The striking low-grade biphasic appearance without TP53 mutation confirmed by immunohistochemistry and molecular testing supported the diagnosis of CHEC. This special morphology, which is usually distributed in the superficial part of the tumor, may result in differences between curettage and surgical specimens. Recent studies have documented an aggressive clinical course in a significant proportion of cases. More cases are needed to establish the clinical behaviors, pathologic features, and molecular profiles of CHECs. Recognition of the relevant characteristics is the prerequisite for pathologists to make correct diagnoses and acquire comprehensive interpretation.

Endometrioid adenocarcinoma of the rectovaginal septum: A case report / 中南大学学报(医学版)

Primary endometrioid adenocarcinoma of the rectovaginal septum is rare. Its pathogenesis is not clear and there is no standard treatment. One patient with endometrioid adenocarcinoma of the rectovaginal septum arising from deep infiltrative endometriosis was admitted to Qingdao Municipal Hospital. The patient presented with incessant menstruation and abdominal distension. She had bilateral ovarian endometriotic cystectomy 6 years ago. Imaging findings suggested a pelvic mass which might invade the rectovaginal septum. Pathological results of primary surgery confirmed endometrioid carcinoma of the pelvic mass arising from the rectovaginal septum. Then she had a comprehensive staged surgery. Postoperative chemotherapy was given 6 times. No recurrence or metastasis was found during the 2-year follow-up. The possibility of deep infiltrating endometriosis and its malignant transformation should be considered in the differential diagnosis of a new extragonadal pelvic lesion in a patient with a history of endometriosis, which would avoid misdiagnosis and missed diagnosis.

Pólipo endometrial metaplásico: hallazgo histeroscópico de enfermedad premaligna en mujeres jóvenes. Reporte de tres casos / Endometrial metaplastic polyps: findings of premalignant disease on histeroscopy in young women, a report of 3 cases

ANTECEDENTES: Los pólipos endometriales son sobrecrecimientos de la mucosa endometrial, una de las causas más comunes de hemorragia uterina anormal, pueden estar asociados con lesiones premalignas y malignas del endometrio. Existen características histeroscópicas que ayudan a diferenciar una lesión benigna o maligna. El pólipo metaplásico es un hallazgo histeroscópico caracterizado por superficies laminares e hiperqueratosis, con zonas blancas e hiperrefringentes. CASOS CLÍNICOS: Tres casos clínicos de pacientes menores de 40 años, con hemorragia uterina anormal donde el hallazgo histeroscópico común fue el pólipo metaplásico, hallazgo premaligno que se confirmó mediante el análisis patológico y la positividad del marcador de inmunohistoquímica p63. Caso 1. Paciente de 28 años, nulípara, obesa, con antecedente de síndrome de ovario poliquístico, con engrosamiento endometrial e histeroscopia, con pólipo con superficie hiperqueratósica, a manera de láminas irregulares, con excrecencias y lesiones exofíticas. Caso 2. Paciente de 25 años, con endometrio irregular engrosado e histeroscopia con hallazgo de pólipos transparentes, con cambios vasculares leves y superficie con zonas hiperrefringentes blanquecinas. Caso 3. Paciente de 38 años, con antecedente de síndrome de ovario poliquístico y obesidad. En la histeroscopia el endometrio se encontró hiperplásico, irregular, con cambios vasculares y pólipos con zonas superficiales hiperrefringentes, sólidas y blancas. CONCLUSIONES: En pacientes jóvenes, con hallazgo histeroscópico de pólipo metaplásico debe considerarse y descartar la enfermedad premaligna y maligna endometrial. El estudio debe completarse con marcadores de inmunohistoquímica (p63), específicos de la metaplasia escamosa.

Abstract BACKGROUND: Endometrial polyps are overgrowths of the endometrial mucosa, one of the most common causes of abnormal uterine bleeding and may be associated with premalignant and malignant endometrial lesions. There are hysteroscopic features that help differentiate a benign or malignant lesion. Metaplastic polyp is a hysteroscopic finding characterized by lamellar surfaces and hyperkeratosis, with white and hyperreflective areas. CLINICAL CASES: Three clinical cases of patients under 40 years of age, with abnormal uterine bleeding where the common hysteroscopic finding was metaplastic polyp, a premalignant finding that was confirmed by pathological analysis and positivity of the immunohistochemistry marker p63. Case 1. 28-year-old female, nulliparous, obese, with a history of polycystic ovary syndrome, with endometrial thickening and hysteroscopy, with polyp with hyperkeratotic surface, in the form of irregular sheets, with excrescences and exophytic lesions. Case 2. 25-year-old patient, with irregular thickened endometrium and hysteroscopy with finding of transparent polyps, with mild vascular changes and surface with whitish hyperrefringent areas. Case 3. 38-year-old patient with a history of polycystic ovary syndrome and obesity. At hysteroscopy the endometrium was found to be irregularly hyperplastic, with vascular changes and polyps with hyper-refringent, solid, white superficial areas. CONCLUSIONS: In young patients, with hysteroscopic finding of metaplastic polyp should be considered and premalignant and malignant endometrial disease should be ruled out. The study should be completed with immunohistochemical markers (p63), specific for squamous metaplasia.

Role of serum microRNAs as biomarkers for endometriosis, endometrioid carcinoma of ovary & endometrioid endometrial cancer

Background & objectives: Accurate and early diagnosis is imperial in the management of endometriosis, endometrioid carcinoma of ovary (ECO) and endometrioid endometrial cancer (EC), yet there are no definitive diagnostic methods available for these diseases. Therefore, the present study was aimed to evaluate the diagnostic potential of differentially expressed miRNAs in serum samples of women with endometriosis, ECO and EC to establish them as diagnostic biomarkers. Methods: Blood samples (5 ml) were obtained from 40 patients (n=10/study group) undergoing laparoscopy/laparotomy/hysterectomy. miRNA-rich RNA was extracted from the serum samples, and quantitative real-time (qRT)-PCR was performed to check the expression levels of miR-16, miR-99b, miR-20a, miR-145, miR-143 and miR-125a in all the samples. Receiver operating characteristic (ROC) curve analysis was done to check the diagnostic potential. Results: In endometriosis, miR-16 was downregulated (P<0.05) whereas miR-99b, miR-125a, miR-143 and miR-145 were upregulated (P<0.05). In ECO group, downregulated expression of miR-16 and miR-125a (P<0.05) was observed, whereas miR-99b, miR-143 and miR-145 were upregulated (P<0.05). In endometrioid EC, miR-16, miR-99b, miR-125 and miR-145 were downregulated (P<0.05), whereas miR-143 was upregulated (P<0.05). ROC curve analysis showed that, for endometriosis, miR-99b, miR-125a, miR-143 and miR-145 served as diagnostic markers. miR-145 showed diagnostic power for ECO, and for endometrioid EC, miR-16, miR-99b, miR-125a and miR-145 showed diagnostic potential. Interpretation & conclusions: The present findings suggested that certain circulating miRNAs (miB99b, miR-16, miR-125a, miR-145) might act as indicators and discriminators of endometriosis and endometrioid subtypes of EC and ovarian cancer and might serve as potential biomarkers for early diagnosis and management of these debilitating diseases.

Incidencia, mortalidad y supervivencia por cáncer de endometrio en Manizales, Colombia 2003-2017 / Incidence, mortality and survival of endometrial cancer in Manizales, Colombia 2003-2017

RESUMEN Objetivo. Estimar la incidencia, mortalidad y supervivencia a cinco años por carcinoma endometrial en Manizales, para el periodo 2003-2017. Materiales y métodos. Estudio observacional, retrospectivo, de base poblacional, con alcance descriptivo. Se ajustaron tasas de incidencia y mortalidad mediante el método directo usando la población mundial Segi como referencia. Se realizó seguimiento pasivo y activo de los casos hasta completar 60 meses o hasta la fecha de cierre de seguimiento. La supervivencia fue estimada mediante funciones de Kaplan-Meier y modelos de regresión de Cox. Resultados. Se observaron 210 casos incidentes en una población de 214 928 mujeres. La edad promedio al diagnóstico fue de 61 años. El tipo histológico más frecuente fue el endometrioide, bien diferenciado. La mayoría de las pacientes estaban afiliadas al régimen contributivo y pertenecían al nivel socioeconómico medio. La tasa de incidencia ajustada por edad fue de 5,7 casos nuevos por cada 100 000 mujeres-año. Se identificaron 75 defunciones con mayor mortalidad entre los 64 y los 79 años. La supervivencia global fue de 95,1% a los 12 meses y de 83,8% a los 60 meses. Se encontraron diferencias estadísticamente significativas en la supervivencia a favor de la histología epitelial, los estadios tempranos al momento del diagnóstico y la edad al diagnóstico menor a 60 años. Conclusiones. La mortalidad es similar a la reportada en otros países de la región. En Manizales, la sobrevida al cáncer de endometrio fue mayor en pacientes con diagnóstico temprano, con edad menor de 60 años y con histología endometrioide.

ABSTRACT Objective. To estimate the incidence, mortality and five-year survival of endometrial carcinoma in Manizales for the period 2003-2017. Materials and methods. Observational, retrospective, population-based study, descriptive in scope. Incidence and mortality rates were adjusted by the direct method using the Segi world population as reference. Passive and active follow-up of the cases was carried out until completing 60 months or until the follow-up closing date. Survival was estimated using Kaplan-Meier functions and Cox models. Results. 210 incident cases were observed in a population of 214.928 women. The average age at diagnosis was 61 years. The most frequent histological type was endometrioid, well differentiated. Most of the patients were affiliated to the contributory health insurance scheme and belonged to the middle socioeconomic level. The age-adjusted incidence rate was 5.7 new cases per 100,000 woman-years. Seventy-five deaths were identified, with greater mortality between 65-69 and 75-79 age groups. Overall survival was 95.1% at 12 months and 83.8% at 60 months. Statistically significant differences were found in survival in favor of epithelial histology, early stages at the time of diagnosis, and age at diagnosis less than 60 years. Conclusions. Manizales follows the global pattern of rise in the age-adjusted incidence rate. Mortality is like that reported in other countries in the region. In Manizales, endometrial cancer survival was higher in patients with early diagnosis, less than 60 years of age, and with endometrioid histology.

Synchronous Endometrioid Endometrial and Serous Ovarian Carcinoma: A double gynecologic jeopardy / Philippine Journal of Obstetrics and Gynecology

@#Synchronous malignant tumors are two primary tumors diagnosed at the same time during surgery. A postmenopausal, nulligravid, presented with vaginal bleeding. Ultrasound revealed an endometrial and right ovarian mass, both with nonbenign features. Cancer Antigen 125 and Human Epididymis Protein 4 were elevated. She underwent extrafascial hysterectomy with bilateral salpingo-oophorectomy with the frozen section of the endometrium and right ovary, followed by complete surgical staging. Histopathology report was endometrioid endometrial carcinoma and high-grade serous ovarian carcinoma. The endometrial and ovarian tissues tested positive for vimentin and Wilm's Tumor 1 (WT1), respectively, suggesting both are primary independent tumors. The pelvic lymph nodes and recto-sigmoid lymph nodes tested positive for vimentin and negative for WT1, suggesting endometrial tumor metastasis. The final diagnosis is synchronous endometrioid endometrial carcinoma Stage IIIC1 and high-grade serous ovarian carcinoma Stage IA, right ovary.

Endometrial cancer with implantation metastasis to vagina: a case report

Authors present a case of vaginal implantation metastasis following a diagnosis of endometrial cancer. A 58-year-old lady presented with postmenopausal bleeding and was later diagnosed to have endometrial cancer. She underwent an extra-fascial hysterectomy and bilateral salpingo-oophrorectomy with pelvic lymphadenectomy for Stage 3A endometrioid adenocarcinoma of the endometrium. The lymph nodes and cervix were free from the disease and no lymphovascular invasion was seen on the pathological specimen. She defaulted adjuvant radiotherapy and was lost to follow up. Six months later she had a tumour recurrence at the vaginal introitus just below the urethral orifice and awal from the vaginal vault with similar histopathological findings as previous cancer. This case highlights the rare occurrence of implantation metastasis of endometrial cancer.

A report of two cases of dedifferentiated endometrioid carcinoma: A newly described underrecognized tumor of poor prognosis

Dedifferentiated endometrioid carcinoma or dedifferentiated endometrioid adenocarcinoma (DEAC) is defined by the presence of undifferentiated carcinoma with endometrioid carcinoma. Undifferentiated component can be misinterpreted as solid component of high-grade endometrioid carcinoma or sarcomatous component of malignant mixed mullerian tumor. We present two cases of DEAC. Two postmenopausal women underwent hysterectomy for vaginal bleeding. Microscopically, sections from the endometrial tumors showed a biphasic growth consisting of an undifferentiated component and a glandular component with sharp transition between the two components. The undifferentiated component showed focal positivity for cytokeratin and vimentin, while glandular component was diffusely positive for cytokeratin and negative for vimentin expression.

Characteristic and clinical significance of microRNA expression between 144 Uygur and Han women with endometrial carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To compare the expression patterns of microRNA (miRNA) between 144 Uygur and Han women with endometrial carcinoma and to investigate their clinical significance.@*METHODS@#Taqman miRNA low-density array was used to compare miRNA profiles between Uygur and Han women with non-endometrioid endometrial carcinoma (NEEC). Five miRNAs were further analyzed in the 144 endometrial cancers including 62 Uygur and 82 Han samples via real-time PCR to determine their expression patterns.@*RESULTS@#MiRNA expression profiles revealed that many miRNAs overexpressed or downregula-ted in one ethnic group, but did not express or changed slightly in the other ethnic group. Further detection in the 144 endometrial cancers showed that miR-141, miR-200a, and miR-205 overexpressed in both ethnic groups. In Uygur endometrioid endometrial carcinoma (EEC), tumors with miR-141/200a overexpression tended to be more aggressive in behavior, whereas in the Han group, EEC with miR-200a overexpression was relative mild. However, the NEEC with miR-200a overexpression also had aggressive clinicopathologic features in the Han women. MiR-145 and miR-143 expressed differentially between Uygur and Han groups, they overexpressed in the former and decreased in the latter (P<0.05). In the Uygur women miR-145/143 increased significantly in NEEC and there was a trend that NEEC exhibiting favorable clinicopathologic factors had higher miR-145 expression, and was statistically significant in tumors with myometrial invasion less than 1/2 thickness (P=0.042). By contrary, miR-145/143 decreased in Han group and EEC with worse clinicopathologic variables had lower expression although without statistical significance. NEEC in Han group had no such tendency.@*CONCLUSION@#Uygur and Han women might have different miRNA expression profiles. MiR-141/200a/205 overexpressed in endometrial carcinomas and miR-141/200a might behave differently between these two ethnic groups as well as in EEC and in NEEC. Although miR-145/143 showed inverse expression patterns between Uygur and Han women with endometrial cancer, they all exerted tumor suppression effect on endometrial cancer.

Primary broad ligament adenocarcinoma

Primary broad ligament carcinoma is a very rare occurrence with 28 reported cases worldwide, to date. The epidemiology, treatment strategy and prognosis are still uncertain because of the scarcity of cases. Currently, all broad ligament carcinomas are managed similar to epithelial ovarian cancer. We report the case of a 43-year-old female with a prolonged complaint of abdominal pain and intermittent urinary retention, requiring frequent catheterization. She was diagnosed with obstructive right hydroureteronephrosis. The abdominal Contrast Enhanced Computed Tomography (CECT) revealed a well-defined heterogeneous lesion of 2.1х3х3.2cm size in the right lateral and posterior wall of the cervix. An ultrasound (USG)-guided Fine Needle Aspiration Cytology (FNAC) of the mass was done and it was suspected to be malignant. The patient underwent total abdominal hysterectomy, right salpingo-oophorectomy, pelvic lymph-nodal sampling, and peritoneal washing. Histological examination depicted an endometrioid adenocarcinoma of the broad ligament. She received adjuvant chemotherapy, followed by hormonal therapy. It has been five years since her surgery, and she is now alive and disease free.

Padrão histopatológico e incidência de carcinomatose peritoneal ao diagnóstico em mulheres com câncer de ovário / Histopathological pattern and incidence of peritoneal carcinomatosis at diagnosis in women with ovarian cancer

Objetivo: Descrever o padrão histopatológico e identificar a incidência de carcinomatose peritoneal no momento do diagnóstico de mulheres diagnosticadas com neoplasia de ovário. Métodos: Trata-se de um estudo transversal e descritivo, baseado na análise secundária de dados correspondentes aos prontuários de mulheres adultas com diagnóstico de neoplasia de ovário de um serviço de referência em oncologia clínica. Foram analisados 40 prontuários entre janeiro de 2007 e janeiro de 2017. Resultados: Ao estadiamento segundo o sistema da International Federation of Gynecology and Obstetrics, três mulheres (7,5%) apresentavam estadiamento clínico (EC) II, três (77,5%) estágio ECIII com carcinomatose peritoneal/invasão da pelve e seis (15%) estágio ECIV com metástases à distância, especialmente para pulmão e fígado. Em relação ao padrão histopatológico, 20 mulheres apresentaram adenocarcinoma seroso papilífero de alto grau (50%), 4 (10%) adenocarcinoma seroso papilífero de baixo grau, 3 (7,5%) adenocarcinoma endometrioide, 3 (7,5%) tumor de teca/granulosa, 3 (7,5%) carcinoma de células claras, 3 (7,5%) tumores não classificados, 2 (5%) disgerminoma e 2 (5%) com cistoadenocarcinoma mucinosos. Conclusão: É nítida a necessidade de mais estudos envolvendo essa patologia, de modo a favorecer o diagnóstico e a intervenção em estágios mais precoces e reduzir desfechos desfavoráveis. (AU)

Objective: To describe the histopathological pattern, and to identify the incidence of peritoneal carcinomatosis at the time of the diagnosis of women diagnosed with ovarian neoplasm. Methods: This is a cross-sectional and descriptive study, based on the secondary analysis of data corresponding to the medical records of adult women diagnosed with ovarian neoplasm in a reference service of clinical oncology. A total of 40 medical records were analyzed between January 2007 and January 2017. Results: At the staging (FIGO system) of the International Federation of Gynecology and Obstetrics, three women (7.5%) had clinical staging (EC) II staging, 31 (77.5%) were in the ECIII stage, with peritoneal carcinomatosis/pelvic invasion, six (15%) were in the ECIV stage, with metastases at a distance, especially to lung and liver. Regarding the histopathological pattern, twenty women had high-grade papillary serous adenocarcinoma (50%), 4 (10%) with low-grade papillary serous adenocarcinoma, 3 (7.5%) with endometrioid adenocarcinoma, 3 (7.5%) with granulosa-theca tumor, 3 (7.5%) with clear cell carcinoma, 3 (7.5%) with unclassified tumors, 2 (5%) with dysgerminoma, two (5%) with mucinous cystadenocarcinoma. Conclusions: There is a clear need for further studies involving this pathology, in order to favor diagnosis and intervention at earlier stages and to reduce unfavorable outcomes. (AU)

Clinical comparison between neuroendocrine and endometrioid type carcinoma of the uterine corpus / 부인종양

OBJECTIVE: To compare the clinicopathologic features and survival outcomes of neuroendocrine tumor of the uterine corpus (NET-U) to endometrioid type endometrial carcinoma (EC). METHODS: From 1993 to 2012, the Surveillance, Epidemiology and End Results cancer registry was queried for women diagnosed with EC or NET-U. Data regarding stage, grade, presence of extra-uterine disease, lymph node metastasis, receipt of adjuvant radiation, surgical intervention and overall survival (OS) was extracted. Chi-square tests, t-tests and Kaplan Meir curves were used for statistical analysis. RESULTS: A total of 98,363 patients were identified: 98,245 with EC and 118 with NET-U. The mean age at diagnosis for EC was 61.7 years and 64.8 years for NET-U (p=0.01). NET-U cases were more likely to be poorly differentiated (97.0% vs. 15.6%; p≤0.01) and have nodal metastasis (56.4% vs. 11.1%; p≤0.01) when compared to EC. Presence of extrapelvic disease at the time of diagnosis was observed more frequently in NET-U compared to EC, 49.1% vs. 4.8%, respectively (odds ratio=18; 95% confidence interval=13.1–27.2; p≤0.01). Significant improvement in OS was observed in NET-U patient who received radiation (OS: 7.7 vs. 3.3 years; p≤0.01) or underwent surgical management (5.6 vs. 0.9 years; p≤0.01). The OS for EC was 14.4 vs. 4.6 years for NET-U (p≤0.01). CONCLUSION: NET-U represents an aggressive form of uterine malignancy. When compared to EC, patients with NET-U present at more advanced stage, have more frequent extra-uterine disease and lower OS.

High Expression of Galectin-1, VEGF and Increased Microvessel Density Are Associated with MELF Pattern in Stage I-III Endometrioid Endometrial Adenocarcinoma

BACKGROUND: In this study, we investigate the expression of markers of angiogenesis and microvessel density (MVD) in cases of microcystic, elongated and fragmented (MELF) pattern, with its prognostic role in the survival of endometrioid endometrial adenocarcinomas (EA) patients. METHODS: In this study, 100 cases of EA, 49 cases with MELF pattern and 51 without, were immunohistochemically stained for galectin-1, vascular endothelial growth factor (VEGF), and MVD. Morphometry and statistical (univariate and multivariate) analyses were performed to assess overall survival (OS) and disease-free survival. RESULTS: The expression of VEGF (p<.001) and galectin-1 (p<.001), as well as MVD area (p<.001) and number of vessels/mm² (p<.050), were significantly higher in the +MELF pattern group compared to the –MELF group. A low negative correlation between MELF-pattern and the number of days of survival (p<.001, r=–0.47) was also found. A low positive correlation of MELF-pattern with galectin-1 expression (p<.001, r=0.39), area of vessels/mm² (p<.001, r=0.36), outcome of EA (p<.001, r=0.42) and VEGF expression (p<.001, r=0.39) suggests potential pathological relevance of these factors in the prognosis of EA. A univariate survival analysis indicated a role for all parameters of survival. Multivariate Cox proportional hazard regression analysis revealed that only area of vessels/mm² (hazard ratio [HR], 1.018; 95% confidence interval [CI], 1.002 to 1.033), galectin-1 (HR, 1.049; 95% CI, 1.025 to 1.074) and VEGF (HR, 1.049; 95% CI, 1.022 to 1.077) play key roles in OS. CONCLUSIONS: This study reports an increase in MVD, VEGF and galectin-1 expression in EA with MELF pattern and suggests that MELF pattern, along with the angiogenic profile, may be a prognostic factor in EA.

Expression of cluster proteins in endometrial carcinoma and its relationship with ER and PR / 中国基层医药

Objective To investigate the expression of cluster proteins in endometrial cancer tissues and its correlation with estrogen receptor ( ER) and progesterone receptor ( PR).Methods We selected 120 cases of endometrial cancer tissue specimens and 120 cases of normal endometrial tissue specimens from January 2013 to December 2017 in the Maternal and Child Health Hospital of Huzhou.The expression of cluster proteins ,ER and PR in tissues were determined by immunohistochemistry.Results The positive rate of cluster proteins in the endometrial carcinoma tissues(89.2%) was higher than that in the normal endometrial tissues (13.3%) ( χ2 ＝145.067,P＜0.05).The positive expression rates of ER and PR in the endometrial carcinoma tissues (60.0%,56.7%) were lower than those in the normal endometrial tissues (100.0%,100.0%) (χ2 ＝93.490,96.698,all P＜0.05).The cluster proteins was negatively correlated with ER and PR in the endometrial carcinoma tissues ( r＝－0.472,－0.513,all P＜0.05).The expression of cluster protein and ER in the endometrial carcinoma were associated with FIGO stage , depth of myometrial invasion and lymph node metastasis of endometrial carcinoma (83.1% vs.93.0%,82.6% vs. 98.0%,97.6% vs.84.6%;81.7% vs.29.2%,91.3% vs.17.6%,19.5% vs.82.1%) ( χ2 ＝6.628,7.228, 4.779;33.062,66.292,43.984,all P＜0.05),and were not associated with age ,degree of differentiation and tumor diameter (all P＞0.05).The positive expression of PR in the endometrial carcinoma was correlated with the FIGO stage and depth of myometrial invasion of the endometrial carcinoma (78.9% vs.24.5%,84.1% vs.20.0%,χ2 ＝34.919,48.577,all P＜0.05),and were not associated with age ,degree of differentiation,tumor diameter and lymph node metastasis (all P＞0.05).Conclusion The development of endometrial cancer is related to the overexpression of cluster proteins,and the expression of cluster proteins may be regulated by estrogen and progesterone .

Multiple model parameters of intravoxel incoherent motion in differentiation of stage endometrial carcinoma and endometrial polyp / 中国医学影像技术

Objective: To investigate the value of the multiple model parameters of intravoxel incoherent motion (IVIM) in identification of stage endometrial carcinoma (EC) and endometrial polyp (EP). Methods: The clinical and imaging data of 31 patients with stage EC (group EC) and 14 patients with EP (group EP), confirmed by postoperative pathological examination, were retrospectively analyzed, all patients were performed on 1.5T MR (including IVIM sequence, b=0, 20, 50, 100, 150, 200, 400, 800, 1 200, 2 000, 3 000 s/mm2) before operation. The IVIM multi-model parameter values of the lesions were measured and compared between the two groups, including the standard apparent diffusion coefficient (ADC-stand), slow-apparent diffusion coefficient (ADC-slow), fast-apparent diffusion coefficient (ADC-fast), perfusion fraction (f), distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α). The ROC curve was used to evaluate the differential diagnostic efficacy of IVIM parameters for stage EC and EP. Results: The ADC-stand value, ADC-slow value, f-value, DDC value and α value of the EC group were all less than the EP group, and the ADC-fast value was greater than the EP group (all P=0.001). ROC curve results showed the standard ADC value, ADC-slow value, ADC-fast value, f value, DDC value and α value had differential diagnostic value for stage EC and EP, the AUC was 0.885, 0.877, 0.919, 0.926, 0.906 and 0.902, respectively (all P<0.05). Conclusion: The multi-model parameters of IVIM sequence can effectively identify stage EC and EP.

The prognostic significance of estrogen and progesterone receptors in grade I and II endometrioid endometrial adenocarcinoma: hormone receptors in risk stratification / 부인종양

OBJECTIVES: Although patients with grade I and II endometrioid endometrial adenocarcinoma (EEA) are considered with good prognosis, among them 15%–25% died in 5 years. It is still unknown whether integrating estrogen receptor (ER) and progesterone receptor (PR) into clinical risk stratification can help select high-risk patients with grade I–II EEA. This study was to investigate the prognostic value of ER and PR double negativity (ER/PR loss) in grade I–II EEA, and the association between ER/PR loss and The Cancer Genome Atlas (TCGA) classification. METHODS: ER and PR were assessed by immunohistochemistry on hysterectomy specimens of 903 patients with grade I–II EEA. ER and PR negativity were determined when < 1% tumor nuclei were stained. Gene expression data were obtained from the TCGA research network. RESULTS: Compared with ER or PR positive patients (n=868), patients with ER/PR loss (n=35) had deeper myometrial infiltration (p=0.012), severer FIGO stage (p=0.004), and higher rate of pelvic lymph node metastasis (p=0.020). In univariate analysis, ER/PR loss correlated with a shorter progression-free survival (PFS; hazard ratio [HR]=5.25; 95% confidence interval [CI]=2.21–12.52) and overall survival (OS; HR=7.59; 95% CI=2.55–22.60). In multivariate analysis, ER/PR loss independently predicted poor PFS (HR=3.77; 95% CI=1.60–10.14) and OS (HR=5.56; 95% CI=1.37–22.55) for all patients, and poor PFS for patients in stage IA (n=695; HR=5.54; 95% CI=1.28–23.89) and stage II–IV (n=129; HR=5.77; 95% CI=1.57–21.27). No association was found between ER/PR loss and TCGA classification. CONCLUSION: Integrating ER/PR evaluation into clinical risk stratification may improve prognosis for grade I–II EEA patients.

Clinical application of TCGA molecular classification in endometrial endometrioid carcinoma / 中华病理学杂志

Objective@#To explore molecular characteristics of endometrial endometrioid cancer according to The Cancer Genome Atlas (TCGA) based molecular classification of endometrial carcinomas and to confirm simple and clinically applicable surrogate methodologies in pathological practice.@*Methods@#Two hundred and twenty-eight cases of endometrial endometroid adenocarcinomas (EnACs) collected from August 2001 to August 2017 from Peking University Health Science Center, Peking University Third Hospital were molecularly categorized by using Sanger sequencing for the exonuclease domain mutations (EDM) of POLE, and by immunohistochemistry for p53 and mismatch repair (MMR) proteins. The cohort was classified into polymerase-E exonuclease domain mutation (POLE EDM), mismatch repair deficiency (MMR-D), p53 abnormal (p53-abn) and p53 wild type (p53-wt) groups. The correlation between molecular subgroups and the clinical-pathological features including prognosis were analyzed.@*Results@#The cohort was distributed as follows: 11(4.8%) POLE EDM, 47(20.6%) MMR-D, 9(4.0%) p53-abn and 161(70.6%) p53-wt. p53-wt subgroup patients demonstrated significantly higher lymph node metastasis (P=0.011) and more advanced stage (P=0.036) than those of somatic hypermutation group cases (POLE EDM and MMR-D). In the FIGO grade 2-3 EnACs cohort, TCGA molecular subtyping was significantly correlated with progression-free survival and overall survival (P=0.043). POLE EDM subgroup had the best survival, while p53-abn subgroup had the worst.@*Conclusions@#Identification of POLE EDM and MMR-D subgroups provides independent and highly valuable prognostic information beyond established histological classification. Based on immunohistochemistry of MMR, p53 and POLE mutational analysis, this pragmatic molecular classification scheme can be served as a reliable surrogate for TCGA molecular classification, which has potential to be used routinely in Chinese pathological practice.

Expression of cluster proteins in endometrial carcinoma and its relationship with ER and PR / 中国基层医药

Objective@#To investigate the expression of cluster proteins in endometrial cancer tissues and its correlation with estrogen receptor (ER) and progesterone receptor (PR).@*Methods@#We selected 120 cases of endometrial cancer tissue specimens and 120 cases of normal endometrial tissue specimens from January 2013 to December 2017 in the Maternal and Child Health Hospital of Huzhou.The expression of cluster proteins, ER and PR in tissues were determined by immunohistochemistry.@*Results@#The positive rate of cluster proteins in the endometrial carcinoma tissues(89.2%) was higher than that in the normal endometrial tissues(13.3%) (χ2=145.067, P<0.05). The positive expression rates of ER and PR in the endometrial carcinoma tissues(60.0%, 56.7%) were lower than those in the normal endometrial tissues(100.0%, 100.0%) (χ2=93.490, 96.698, all P<0.05). The cluster proteins was negatively correlated with ER and PR in the endometrial carcinoma tissues (r=-0.472, -0.513, all P<0.05). The expression of cluster protein and ER in the endometrial carcinoma were associated with FIGO stage, depth of myometrial invasion and lymph node metastasis of endometrial carcinoma(83.1% vs.93.0%, 82.6% vs.98.0%, 97.6% vs.84.6%; 81.7% vs.29.2%, 91.3% vs.17.6%, 19.5% vs.82.1%) (χ2=6.628, 7.228, 4.779; 33.062, 66.292, 43.984, all P<0.05), and were not associated with age, degree of differentiation and tumor diameter (all P>0.05). The positive expression of PR in the endometrial carcinoma was correlated with the FIGO stage and depth of myometrial invasion of the endometrial carcinoma(78.9% vs.24.5%, 84.1% vs.20.0%, χ2=34.919, 48.577, all P<0.05), and were not associated with age, degree of differentiation, tumor diameter and lymph node metastasis (all P>0.05).@*Conclusion@#The development of endometrial cancer is related to the overexpression of cluster proteins, and the expression of cluster proteins may be regulated by estrogen and progesterone.