ADAMTS proteoglycanases downregulation with impaired oocyte quality in PCOS

ABSTRACT Objective: A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) and ADAMTS-5 normal expression levels are essential for ovulation and subsequent fertilization. The objective of the present study was to assess expression pattern of these genes in cumulus cells (CCs) taken from patients with polycystic ovary syndrome (PCOS) and to investigate any possible relationship with the oocyte quality. Subjects and methods: ADAMTS-4 and -5 expression levels within CCs containing oocytes at the metaphase II (MII) and germinal vesicle (GV) stages, taken from 35 patients with PCOS and 35 women with normal ovarian function, were investigated using RT-qPCR. Moreover, possible correlations between ADAMTS-4, ADAMTS-5, and progesterone receptors (PRs) expression as well as oocyte quality were evaluated. Results: ADAMTS-4 and -5 expression levels were dramatically diminished in the CCs of the PCOS patients when compared to the controls. ADAMTS-4 and -5 expression levels were correlated with each other and with the oocyte quality. Furthermore, lower expression levels of ADAMTS-4 and -5 in the PCOS patients were strongly correlated with the diminished PRs expression levels. Conclusions: Downregulation of ADAMTS-4 and -5 in the human CCs of the PCOS patients correlated with the decline in the PRs expression, and impaired oocyte quality may cause lower oocyte recovery, maturation, and fertilization rate.

Clinico-pathological study of locally advanced breast cancer and their hormone receptor analysis

Background: Breast carcinoma is one of the most common malignant tumor of women. Determination of estrogen receptors (ER) and progesterone receptors (PR) status, prior to therapeutic intervention has become standard practice. Survival and response to hormone therapy are most favorable among women who are receptor positive. The aim of this study is to assess the hormone receptor status in locally advanced breast carcinomas and correlate this reactivity pattern with tumor stage, clinical stage and lymph node metastasis. Objective of the study was to co-relate the locally advanced breast cancer and their hormone receptor analysis.Methods: Patients who visited Department of General Surgery, Hamidia Hospital, Bhopal were assessed clinically, radiologically and histopathologically and then ER and PR study was done, for a total of 50 cases were done.Results: In our study majority of the cases were locally advanced breast cancer (50%) which may be due to the low socio economic status, late presentation, pain tolerance, illiteracy and availability of the resources. Majority of cases were in postmenopausal, clinical stage 3 and histological grade 2. ER positivity 50% and PR positivity 44% and it was found that hormone receptor positivity was high in locally advanced breast cancers 63.5%.Conclusions: Hormone receptor analysis should be an integral part of initial workup of carcinoma breast, as the percentage of hormone receptor positivity is increasing in our population in locally advanced breast cancer. So locally advanced breast cancer can be diagnosed at an early stage by screening and conducting breast awareness programs.

Progesterone and estradiol receptors and Ki-67 in the superficial and deep infiltrating endometriosis / Receptores de progesterona e estradiol e Ki-67 no estroma e no epitélio de endometriose superficial e profunda

ABSTRACT Introduction: Endometriosis is a hormone-dependent disease characterized by ectopic presence of endometrial tissue responsive to ovarian steroids. Estrogen and progesterone are the main regulators of endometrial tissue, and the expression of receptors of these hormones in the ectopic tissue seems to be related to the pathophysiology of the disease. Ki-67 is a marker of tissue proliferation and an important marker of epithelial kinetics. Endometriosis can be classified as superficial, in the peritoneum, and deep, when it extends into ligaments and other organs. Objective: Our objective was to analyze the expression of estrogen and progesterone receptors and Ki-67, through immunohistochemistry, in different sites of endometriosis tissues (superficial peritoneal/ovarian endometriosis and deep infiltrating endometriosis). Casuistic and methods: We studied nine patients; five with superficial and four with deep endometriosis. Statistical correlation was performed with the Shapiro-Wilk test (significance level of 5%) and linear correlation analysis using Spearman's non-parametric test (significance of 1%). There was a correlation of Spearman between the estrogen receptor variable and Ki-67 in patients with superficial endometriosis. There was also a correlation between the variables estrogen receptor and progesterone receptor in patients with deep endometriosis. Results: Contrary to what was found for superficial endometriosis, there is linear increase of the variables, with a strong and positive correlation coefficient. This demonstrates that the variation of estrogen receptors can be explained in 99.1% by the same variation of progesterone receptors in deep endometriosis. Conclusion: It is possible to infer that other factors are involved in the response to hormonal variations for superficial and deep endometriosis.

RESUMEN Introducción: Endometriosis es una enfermedad dependiente de hormonas que se caracteriza por la presencia ectópica de tejido endometrial sensible a los esteroides del ovario. El estrógeno y la progesterona son los principales reguladores del tejido endometrial, y la expresión de receptores de esas hormonas en el tejido ectópico parece tener conexión con la fisiopatología de la enfermedad. El Ki-67 es un marcador de proliferación tisular y de la cinética epitelial. La endometriosis puede ser clasificada en superficial y profunda, alcanzando ligamentos y otros órganos. Objetivo: El objetivo de este estudio fue analizar la expresión de los receptores de estrógeno y progesterona y Ki-67, mediante inmunohistoquímica en endometriosis superficial peritoneal/ ovárica y endometriosis infiltrativa profunda. Casuística y métodos: Estudiamos nueve casos: cinco de endometriosis superficial y cuatro de endometriosis profunda. La correlación estadística fue realizada con el test de Shapiro-Wilk (nivel de significación del 5%), y el análisis de correlación linear, por la prueba no paramétrica de Spearman (nivel de significación del 1%). Hubo correlación de Spearman entre la variable receptor de estrógeno (RE) y Ki-67 en pacientes con endometriosis superficial, y entre las variables RE y receptor de progesterona (RP) en pacientes con endometriosis profunda. Resultados: Al contrario de lo que se ha encontrado para endometriosis superficial, hay aumento lineal de las variables, con coeficiente de correlación fuerte e positivo. Eso demuestra que la variación de los receptores para estrógeno puede ser explicada en el 99,1% por la misma variación de los RP en la endometriosis profunda. Conclusión: Es posible deducir que otros factores estén involucrados en las diferentes respuestas hormonales para endometriosis superficial y profunda.

RESUMO Introdução: Endometriose é doença hormônio-dependente caracterizada pela presença ectópica de tecido endometrial responsivo aos esteroides ovarianos. O estrogênio e a progesterona são os principais reguladores do tecido endometrial, e a expressão de receptores desses hormônios no tecido ectópico parece ter relação com a fisiopatologia da doença. O Ki-67 é um marcador de proliferação tecidual e importante sinalizador da cinética epitelial. A endometriose pode ser classificada em superficial e profunda, atingindo ligamentos e outros órgãos. Objetivo: O objetivo deste estudo foi analisar a expressão dos receptores de estrógeno e progesterona e Ki-67, por meio de imuno-histoquímica em endometriose superficial peritoneal/ovariana e endometriose infiltrativa profunda. Casuística e métodos: Estudamos nove casos, cinco de endometriose superficial e quatro de endometriose profunda. A correlação estatística foi efetuada com os testes de Shapiro-Wilk (nível de significância 5%) e a análise de correlação linear, pelo teste não paramétrico de Spearman (1% de significância). Houve correlação de Spearman entre a variável receptor de estrogênio (RE) e Ki-67 em pacientes com endometriose superficial e entre as variáveis RE e receptor de progesterona (RP) em pacientes com endometriose profunda. Resultados: Ao contrário do que foi encontrado para endometriose superficial, há o aumento linear das variáveis, com coeficiente de correlação forte e positivo. Isso demonstra que a variação dos receptores para estrogênio pode ser explicada em 99,1% pela mesma variação dos RP na endometriose profunda. Conclusão: É possível inferir que estejam envolvidos outros fatores nas diferentes respostas hormonais para endometriose superficial e profunda.

Carcinoma ductal in situ de la mama con características apocrinas: reporte de un caso / Ductal carcinoma in situ of the breast with apocrine characteristics: case report

Resumen Se presenta el caso de una femenina de 69 años con un carcinoma ductal in situ de la mama, el cual presentaba diferenciación apocrina y alto grado nuclear. La forma de presentación clínica se hizo patente en forma de microcalcificaciones detectadas en la mamografía, y corroboradas histológicamente como comedonecrosis. La diferenciación apocrina se comprobó por medio de tinciones de inmunohistoquímica. El diagnóstico se realizó en una biopsia excisional, pero dado a que uno de los márgenes se encontraba comprometido, la paciente se sometió posteriormente a una mastectomía.

Abstract We present the case of a 69 year old female diagnosed with a ductal in situ carcinoma of the breast. The tumor had apocrine differentiation and a high nuclear grade. The clinical presentation corresponded to microcalcifications detected on mammography, which were histologically patent in the form of comedo type necrosis. The aforementioned apocrine differentiation was reassured using the aid of immunohistochemistry. The biopsy was an excisional biopsy, but due to positive quirurgical margins, the patient was later reintervened for total mastectomy.

Omitting Adjuvant Radiotherapy for Hormone Receptor‒Positive Early-Stage Breast Cancer in Old Age: A Propensity Score Matched SEER Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the non-inferiority of omitting radiotherapy (RT) after breast-conserving surgery (BCS) for hormone receptor (HR)‒positive T1N0 breast cancer in elderly women. MATERIALS AND METHODS: From 2004 to 2014, HR-positive T1N0 breast cancer patients aged 50 years or older and receiving BCS were retrieved from the Surveillance, Epidemiology, and End RESULTS: 18 database. After propensity score matching between the no-RT and RT groups, univariate and multivariate analyses were performed. Identified prognostic factors were used to stratify the risk groups. In each risk group, 10-year cancer-specific survival (CSS) rates were compared between the no-RT and RT groups. RESULTS: After propensity score matching, the numbers of patients in the no-RT and RT groups were both 18,586. For patients who satisfied both a tumor size of 1-10 mm and a tumor grade of 1-2, omitting RT did not decrease the CSS rate at any age group, ranging from ≥ 50 to ≥ 85 years; for patients aged ≥ 50 years, the 10-year CSS rates in the no-RT and RT groups were 97.2% and 96.8%, respectively (adjusted hazard ratio, 0.862; p=0.312). However, for patients with a tumor size of 11-20 mm or tumor grade of 3-4, RT significantly increased the CSS rate irrespective of age. CONCLUSION: RT after BCS for HR-positive T1N0 breast cancer in elderly women might be omitted without causing a decrease in the CSS rate, but only in patients who satisfy both a small tumor size (≤ 10 mm) and low tumor grade (1-2).

Treatment Outcomes of Weakly Positive Hormone Receptor Breast Cancer and Triple-Negative Breast Cancer

PURPOSE: In breast cancer, response to endocrine therapy depends on estrogen receptor and progesterone receptor status. However, poor prognosis is conferred on patients with hormone receptor (HR)-positive breast cancer. We aimed to examine weakly positive HR breast cancer by comparing weakly positive HR to strongly positive HR and negative HR breast cancer. METHODS: We examined the clinical and biological features of 1,496 women with breast cancer, and these patients were categorized according to HR status as weakly positive, strongly positive, and negative HR breast cancer. RESULTS: In this study, among 1,496 patients with breast cancer, negative HR breast cancer was found in 374, weakly positive HR breast cancer in 90 and strongly positive HR breast cancer in 1,032 patients. Our multivariate analysis showed that there were differences in T stage, tumor-node-metastasis stage, vascular invasion, histologic grade and type, and Ki-67 index. Patients with weakly positive HR breast cancer had an increased risk of death and recurrence compared with those with strongly positive HR breast cancer and had similar prognosis as patients with negative HR breast cancer. CONCLUSION: Patients with weakly positive HR breast cancer received endocrine therapy because they were regarded as having positive HR breast cancer. However, their prognosis of overall survival and relapse-free survival was similar to that in patients with negative HR breast cancer. Therefore, we need to closely observe and consider active treatment for patients with weakly positive breast cancer.

Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST. MATERIALS AND METHODS: The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup. CONCLUSION: ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.

Prognostic Value of Estrogen and Progesterone Receptor Expression in Low Proliferative Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

PURPOSE: Approximately two-thirds of breast cancer are estrogen-dependent cancers, which express estrogen receptor (ER)/progesterone receptor (PR). We investigated the prognostic value of ER/PR expression in human epidermal growth factor receptor 2 (HER2)-negative and low proliferative (Ki-67 ≤20%) breast cancer. METHODS: A retrospective review was performed of 252 breast cancer data records, identified as ER/PR-positive, low Ki-67 proliferation index (≤20%) and HER2-negative. The data were divided into two subgroups: a strong luminal subgroup and a weak luminal subgroup, according to hormonal receptor expression status. Outcome measures included age at diagnosis, tumor size, tumor-node-metastasis (TNM) stage, ER, PR, Bcl-2, recurrent or metastatic characteristics, disease-free survival and overall survival, of each subgroup. RESULTS: There were no statistical differences in TNM stage or tumor numbers between the two subgroups. The strong luminal subgroup was associated with a higher Bcl-2 expression (p<0.001). The weak luminal subgroup was associated with more frequent neural invasion (p=0.051) and lung (p=0.031), liver (p=0.031) and brain (p=0.033) metastases, than the strong luminal subgroup. Disease-free survival was significantly longer in the strong luminal subgroup than weak luminal subgroup (p=0.015). Overall survival was also significantly improved in the strong luminal subgroup relative to the weak luminal subgroup (p=0.014). CONCLUSION: The weak luminal subgroup showed worse prognosis than the strong luminal subgroup, among ER/PR-positive HER2-negative low proliferative breast cancer patients. Weak ER or PR expression, can be considered a poor prognostic factor in ER/PR-positive HER2-negative low proliferative breast cancer.

Progesterone upregulates GABAA receptor expression in the sympathetic center of rats with preeclampsia / 第二军医大学学报

Objective To observe the expression of GABAa receptor in rostral ventrolateral medulla (RVLM) of preeclampsia (PE) rats, so as to explore the role of GABAa receptor in the mechanisms by which progesterone improves cardiovascular dysfunction in PE rats. Methods Desoxycorticosterone acetate (DOCA) was intraperitoneally injected and 0. 9% normal saline (NS) replaced the normal drinking water in pregnant rats to establish rat PE model, and the models were verified by measuring the mean arterial pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and concentration of 24-h urine protein. And the modll rats were set as pregnant+DOCA+ saline (PDS) group. The other three groups included the nonpregnant rats (Con) group, nonpregnant rats receiving DOCA and saline (DS) group, and normal pregnant rats (NP) group. The PDS and NP groups were further divided into two subgroups according to different treatments: progesterone (17- OHPC) or NS administration, and the four groups were designated as NP+17-OHPC, NP+Veh, PDS+17-OHPC and PDS+ Veh groups. After three days of 17-OHPC treatment, the levels of progesterone in serum and cerebrospinal fluid were examined by the enzyme-linked immunosorbent assay (ELISA). The MAP, HR, RSNA and the 24-h urine protein were measured. Western blotting analysis was used to detect the protein expressions of GABAa receptor, GABAB receptor, and the nuclear progesterone receptors (nPGRA and nPGRB). Results Compared with Con, DS and NP groups, the MAP, RSNA and 24-h urine protein were increased significantly in PDS group (P<0. 05). Compared with NP group, progesterone levels in the serum and cerebrospinal fluid were significantly decreased in PDS group (P<0. 05). Three days after administration of progesterone to rats in PDS group, the MAP, RSNA and24-h urine protein were significantly reduced (P<0. 05), while the levels of progesterone in the serum and cerebrospinat fluid were significantly increased (P<0. 05). It was found that the expression of the GABAa receptor in RVLM was significantly decreased in PDS group compared with NP group (P<0. 05), which was reversed after 3 days’ administration of progesterone (P<0. 05). Compared with NP group, the expression of nPGRB was significantly increased in RVLM of rats in PDS group (P<0. 05), whereas progesterone treatment for 3 days produced a significant decrease of nPGRB (P<0. 05). The expressions of GABAB receptor and nPGRA were not significantly different between PDS and NP groups. Conclusion The expression of GABAA receptor is decreased in the RVLM of PE rats, which can be reversed by progesterone administration.

A study of triple negative breast carcinomas.

Aim and objectives: To show the incidence of triple negative breast carcinomas in the younger age group (20-40 years) in the study sample and to establish a correlation between expression patterns of estrogen receptor (ER), progesterone receptor (PR) and HER2 /neu with tumour histopathology of breast carcinoma. Material and methods: A 5 years study, 2 years restopective and 3 years prospective was conducted in Mahatama Gandhi Memorial hospital, Warangal, from 2009 to 2014 on triple negative breast carcinomas. All the mastectomy specimens, received in the pathology Department during this period were considered. Results: Total of 28 cases of carcinoma breast in females diagnosed histopathologically, were included in the study. In the present study, the patients were in the age group of 20-40 years Since most carcinomaS in this age group are triple negative. most of the tumours werte of size > 5 cm, 12 cases (43%), followed by 10 cases (36%) of size 2-5 cm. Total 20 (71.4%) were IDC (NOS), followed by 4 (14.2%) were Medullary carcinomas and 2 (7.1%) cases of ILC and each 1 (3.6%) case of tubular and Mucinous carcinomas. Histopathological grading was done according to Modified Bloom Richardson grading and found that 11 (39.3%) were of grade II followed by 5 (17.9%) cases were grede lll,4 cases were of grade I and 8 cases were inassessible. ER and PR were positive in 61% and 47% of tumors respectively. HER-2 over expression was seen in 36% of tumors and was negative in 64% of tumours. Triple negative carcinomas were 4 out of 28 cases, of which 3 were IDC (NOS) and 1 was medullary carcinoma. Triple negative carcinomas are associated with poor prognosis. Conclusion: ER, PR and HER-2 status correlates well with histopathological grading and other clinico-pathological parameters. Higher grade is associated with HER-2 positivity and ER/PR negativity,larger tumor size, lympho-vascular invasion, lymph node metastasis, and higher clinical stage.

Differences in Clinical Outcomes between Luminal A and B Type Breast Cancers according to the St. Gallen Consensus 2013 / 한국유방암학회지

PURPOSE: Human epidermal growth factor receptor 2 (HER2)-positive luminal B type comprises estrogen receptor (ER)-positive and HER2-positive cancers, and HER2-negative luminal B type comprises ER-positive cancers showing a Ki-67 labeling index > or =14% or progesterone receptor (PR) expression of <20% according to the St. Gallen consensus 2013. The current study aimed to classify intrinsic subtypes according to the St. Gallen consensus 2013 and determine the differences in clinicopathological parameters and survival outcomes among the molecular types, especially among the luminal types. METHODS: Assessment of molecular types was performed for 267 invasive ductal carcinomas. The differences in clinicopathological parameters, disease-free survival (DFS), and overall survival (OS) among the molecular types were analyzed. RESULTS: The luminal B type was the most prevalent, at 44.9%, followed by the luminal A, triple-negative (including basal-like type), and HER2 type, at 21.7%, 18.7%, and 14.6%, respectively. There were statistically significant differences in size (p=0.003), nodal status (p=0.046), histologic grade (p<0.001), p53 (p<0.001) and cyclooxygenase 2 (COX-2) positivity (p=0.002), recurrence (p=0.001) and death rates (p=0.036), DFS (p=0.002), and OS (p=0.039) among the molecular types. Significant differences in size (p=0.009), nodal metastasis (p=0.019), histologic grade (p<0.001), p53 positivity (p=0.001), and PR expression (p<0.001) were noted between the luminal A and B types. Among the luminal B type cancers, the distributions of ER and PR scores showed significant differences (p=0.003, p=0.003). p53 positivity in the luminal B type cancers was related to shortened DFS (p=0.034). In luminal type cancers, COX-2 positivity was related to longer DFS (p=0.026). CONCLUSION: Different management guidelines should be considered for the luminal A and luminal B breast cancer types. Positive p53 expression in luminal B type cancers and negative COX-2 expression in luminal type cancers seem to be related to poor clinical outcome.

Expression of Immunohistochemical Markers before and after Neoadjuvant Chemotherapy in Breast Carcinoma, and Their Use as Predictors of Response / 한국유방암학회지

PURPOSE: For patients with breast carcinoma, immunohistochemical markers are important factors in determining the breast cancer subtype and for establishing a therapeutic plan, including the use of neoadjuvant chemotherapy (NACT). However, it is not clear whether the expression of certain markers changes after NACT. METHODS: We assessed estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, and Bcl-2 expression in specimens from 345 breast cancer cases before and after NACT. We analyzed the association between response to NACT and the expression of the markers in pre-NACT specimens. We also compared the expression between pre- and post-NACT specimens. RESULTS: ER and PR expression was negatively associated with pathological complete response (pCR). HER2 was associated with pCR in all cases, but the association was lost when the cases were subdivided according to hormone receptor status. The pre-NACT tumor size of cases with pCR after NACT was smaller than that of cases with residual disease. HER2-enriched and triple-negative breast cancers were more likely to achieve pCR than luminal A type cancers. PR expression and the Ki-67 index decreased after NACT. A decrease in the Ki-67 index was also demonstrated in hormone receptor positive and HER2-enriched subtypes, but no similar tendency was observed in the triple-negative subtype. CONCLUSION: A patient with breast cancer scheduled for NACT should be assessed for the breast cancer subtype, as this will influence the treatment plans for the patient. The expression of PR and Ki-67 after NACT should be interpreted carefully because NACT tends to reduce the expression of these molecules.

Prognostic Role of Interleukin-6, Interleukin-8, and Leptin Levels According to Breast Cancer Subtype / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Inflammation within the tumor microenvironment has been reported to show an association with poor prognosis in breast cancer. However, the associations may differ according to breast cancer subtype. In this study, we investigated the association between inflammation-related markers and breast cancer recurrence according to patients' tumor subtypes. MATERIALS AND METHODS: This prospective study included 240 patients who underwent surgery for management of newly diagnosed breast cancer. Levels of inflammation-related markers (interleukin [IL]-1beta, IL-6, IL-8, monocyte chemoattractant protein-1 [MCP-1], leptin, and adiponectin) were measured at diagnosis, and the associations between these markers and breast cancer recurrence during a six-year follow-up period were examined using the Kaplan-Meier statistical method. RESULTS: Overall, inflammation-related markers showed no association with breast cancer recurrence. However, when data were stratified by tumor subtype, higher levels of some mediators showed an association with poor prognosis among patients with particular subtypes. Compared to patients without recurrence, patients with recurrence had higher levels of circulating IL-6 (p=0.024) and IL-8 (p=0.016) only among those with HER2- tumors and had higher levels of leptin (p=0.034) only among those with estrogen receptor (ER)+/progesterone receptor (PR)+ tumors. Results of survival analyses revealed an association of high levels of IL-6 (p=0.016) and IL-8 (p=0.022) with poor recurrence-free survival in patients with HER2- tumors. In addition, higher leptin levels indicated shorter recurrence-free survival time only among patients with ER+/PR+ tumors (p=0.022). CONCLUSION: We found that certain cytokines could have a differential prognostic impact on breast cancer recurrence according to breast cancer subtype. Conduct of additional large studies will be required in order to elucidate the precise roles of these cytokines in breast cancer progression.

Perfil imuno-histoquímico e variáveis clinicopatológicas no câncer de mama / Immunohistochemical profile and clinical-pathological variables in breast cancer

OBJETIVO: Descrever as principais características em mulheres com câncer de mama, de acordo com o perfil imuno-histoquímico. MÉTODOS: A população foi composta a partir de coorte hospitalar formada por mulheres com diagnóstico de câncer de mama efetuado entre 2003 e 2005 (n = 601) e atendidas em centro de referência em assistência oncológica de Juiz de Fora-MG. Foram selecionadas apenas 397 mulheres que possuíam imunohistoquímica completa. Para definição dos grupos segundo perfil imuno-histoquímico, optou-se por classificação baseada na avaliação dos receptores de estrógeno e de progesterona, índice de proliferação celular Ki67 e superexpressão de HER2. De acordo com os diferentes fenótipos, foram definidos cinco subtipos: luminal A, luminal B-HER2 negativo, luminal B-HER2 positivo, triplo negativo e HER2 superexpresso. RESULTADOS: A maioria dos pacientes tinha pele branca (80,7%) e era pós-menopausada (64,9%), com idade média de 57,4 anos (±13,5). Ao diagnóstico, 57,5% delas tinha tumor de tamanho > 2,0 cm, e 41,7% exibiam comprometimento linfonodal. Os subtipos mais frequentes foram luminal B-HER2 negativo (41,8%) e triplo negativo (24,2%). No subtipo luminal A, 72,1% das pacientes eram pós-menopausadas, enquanto que os maiores percentuais na pré-menopausa foram observados nos subtipos luminal B-HER2 positivo e triplo negativo (45,2% e 44,2%, respectivamente). Verificou-se maior frequência de tumores > 2,0 cm e com linfonodos comprometidos nos subtipos triplo negativo e HER2 positivo. CONCLUSÃO: Esta pesquisa possibilitou avaliar a distribuição das principais características clinicopatológicas e relacionadas aos serviços de saúde em coorte de mulheres brasileiras com câncer de mama, segundo os subtipos tumorais imuno-histoquímicos.

OBJECTIVE: To describe the main characteristics of women with breast cancer, according to the immunohistochemical profile. METHODS: The population comprised a hospital cohort, consisting of women diagnosed with breast cancer between 2003 and 2005 (n = 601) and treated at a referral center for cancer care in Juiz de Fora, MG, Brazil. Only 397 women who had complete immunohistochemistry analysis were selected. To define the groups according to the immunohistochemical profile, the assessment of estrogen and progesterone receptors, Ki-67 cell proliferation index, and overexpression of human epidermal growth factor receptor 2 (HER2) was chosen. According to the different phenotypes, five subtypes were defined: luminal A, luminal B HER2 negative, luminal B HER2 positive, triple negative, and HER2 overexpression. RESULTS: Most patients were white (80.7%) and post-menopausal (64.9%), with a mean age of 57.4 years (± 13.5). At diagnosis, 57.5% had tumor size > 2.0 cm, and 41.7% had lymph node involvement. The most common subtypes were luminal B - HER2 negative (41.8%) and triple negative (24.2%). In the luminal A subtype, 72.1% of patients were post-menopausal, while the highest percentage of premenopausal women were observed in the luminal B - HER2 positive and triple negative subtypes (45.2% and 44.2%, respectively). A higher frequency of tumors > 2.0 cm and lymph node involvement was observed in triple negative and HER2 positive subtypes. CONCLUSION: This study allowed the distribution assessment of the main clinical and pathological characteristics and those related to health services in a cohort of Brazilian women with breast cancer, according to the immunohistochemical tumor subtypes.

Expresión de receptores de estrógenos y progesterona en el tracto genital de ovejas raza Texel / Expression of estrogen and progesterone receptors in the genital tract of Texel ewes

El comportamiento reproductivo de los ovinos varía entre las diferentes razas. Dentro de los factores que inciden en la capacidad reproductiva, el nivel de expresión de receptores de estrógenos y progesterona en su tracto genital parece tener un rol relevante. En el endometrio, oviducto y ovario los estrógenos y progesterona, regulan la expresión de numerosas proteínas comprometidas en su desarrollo morfofuncional. Factores genéticos como la raza estarian relacionados con los niveles de expresión de estos receptores. Las ovejas de raza Texel tienen elevados índices de fertilidad, son muy prolíficas y presentan un alto porcentaje de gestación múltiple lo cual podría tener relación con la expresión de estos receptores en el tracto reproductivo. El objetivo del presente estudio fue evaluar la expresión de receptores de estrógenos y progesterona en tracto genital de ovejas de raza Texel de alta prolificidad. La expresión de la proteína receptora de ambos receptores se detectó mediante análisis inmunohistoquímico y el nivel de expresión de los transcritos por RT-PCR en Tiempo Real Cuantitativo. Los resultados muestran expresión inmunohistoquímica del receptor de estrógeno principalmente en zonas glandulares y carunculares del endometrio. Se destaca además una menor expresión de ambos receptores en ovario, epitelio del oviducto y cervix. La expresión del receptor de progesterona a nivel inmunohistoquímico es bastante menor en cuanto a la señal destacándose marcas débiles en endometrio y ovarios. El nivel de expresión de los transcritos mantiene la misma distribución que las señales inmunohistoquimicas para ambos receptores. Concluimos que ambos receptores son expresados en el sistema reproductivo de ovejas de raza Texel en una distribución similar a lo encontrado en otras razas de ovejas quedando por definir si los niveles de expresión son similares en las distintas razas.

Reproductive performance of sheep varies between different races. Among the factors that affect the reproductive capacity, the level of expression of estrogen and progesterone receptors in the genital tract appears to have a relevant role. In the endometrium, oviduct and ovarian estrogen and progesterone regulate the expression of numerous proteins involved in morphofunctional development. Genetic factors such as race would be related to expression levels of these receptors. The Texel ewes have high fertility rates, are very prolific and have a high percentage of multiple births which could be related to the expression of these receptors in the reproductive tract. The aim of this study was to evaluate the expression of estrogen and progesterone receptors in the genital tract of ewes and Texel high prolificacy. The expression of the receptor protein of both receptors was detected by immunohistochemistry and the level of expression of the transcripts by Quantitative RT-PCR Real-Time. The results showed immunohistochemical expression of estrogen receptor mainly in areas of glandular and caruncular endometrium. It also highlights a lower expression of both receptors in ovarian tissue, epithelium of the oviduct and cervix. Expression of progesterone receptor immunohistochemical level is much lower with weaker signal in endometrium and ovaries. The expression level of transcripts remains the same distribution as immunohistochemical signals for both receptors. We conclude that both receptors are expressed in the reproductive system Texel ewes in a distribution similar to that found in other breeds of sheep, must be defined if the levels of expression are similar in different races.

Expresión de los receptores hormonales (RE/RP) y sobreexpresión de la proteína HER-2/neu en carcinoma ductal infiltrante / The susceptibility to infection by Leishmania panamensis and the sensitivity to drugs differ according to the macrophage type

Introducción: El grado de diferenciación tumoral, la expresión de los receptores de estrógeno y progesterona y la sobreexpresión de la proteína HER-2/neu son factores de tipo pronóstico y predictivo importantes en la evolución y conducta terapéutica del carcinoma mamario infiltrante. Se ha encontrado en diversos estudios que los inmunofenotipos que no expresan los receptores hormonales o que sobre expresan la proteína HER-2/neu se asocian con pobre diferenciación tumoral. Objetivo: Determinar el perfil inmunofenotípico del carcinoma ductal infiltrante y establecer su relación con el grado de diferenciación tumoral. Metodología: Usando técnicas de inmunohistoquímica se determinaron los receptores de estrógeno (RE) y progesterona (RP), y la sobreexpresión de la proteína HER-2/neu en muestras de carcinoma ductal infiltrante y se identificaron sus fenotipos basados en la clasificación de Cheang. La variedad histológica y el grado de diferenciación tumoral en los carcinomas ductales infiltrantes fueron evaluados en tejido coloreado con hematoxilina-eosina. Resultados: Se incluyeron las muestras de 58 pacientes con carcinoma ductal infiltrante. El 15,5% de los carcinomas eran bien diferenciados, 63,8% moderadamente diferenciados y el 20,7% restante pobremente diferenciados. El inmunofenotipo triple negativo se presentó en 29,3% de las muestras, HER2+ en el 20,7%, luminal/ HER2+ en el 1,7%, luminal A en el 43,1% y ER-/PR+/HER2- en el 5,2%. Conclusión: En nuestro estudio, no se encontró asociación entre el grado de diferenciación tumoral y los inmunofenotipos. Salud UIS 2011; 43 (2): 149-158.

Introduction: The degree of tumor differentiation, the expression of estrogen and progesterone receptors and HER-2/ neu protein overexpressing are important prognostic and predictive factors in the evolution and therapeutic management of invasive breast carcinoma. In different studies were found that the immunophenotypes that do not express hormonal receptors or the HER-2/neu protein overexpressing have been associated with poor tumor differentiation. Purpose: To determine the immunophenotypic profile of invasive ductal carcinoma and establish its relationship with the histological grade. Methodology: Using immunohistochemistry were determined the estrogen receptor (ER) and progesterone (PR) and HER-2/neu protein overexpression in invasive ductal carcinoma samples and their phenotypes were identified based on classification of Cheang. The histological subtype and degree of tumor differentiation in invasive ductal carcinomas were evaluated in tissue stained with hematoxylin-eosin. Results: In this study were included 58 patients with invasive ductal carcinoma. 15.5% of the carcinomas were well differentiated, 63.8% moderately differentiated and the remaining 20.7% poorly differentiated. The triple-negative immunophenotype was show in 29.3% of the samples, HER2+ in the 20.7%, luminal/HER2 + in the 1.7%, luminal A in the 43.1% and the phenotype (ER-/PR+/HER2) in the 5.2%. Conclusion: In this study don't was found association between the degree of tumor differentiation and the immunophenotypes. Salud UIS 2011; 43 (2): 149-158.

Patterns of Recurrence after Breast-Conserving Treatment for Early Stage Breast Cancer by Molecular Subtype / 한국유방암학회지

PURPOSE: To study clinical features and patterns of recurrence after breast-conserving treatment (BCT) for three molecular subtypes of early stage breast cancer. METHODS: The sample studied included 596 patients with T1-2N0-1 breast cancer who received BCT. Three groups were defined by receptor status. Luminal: estrogen receptor (ER) or progesterone receptor (PR) positive; triple negative (TN): ER, PR, and epidermal growth factor receptor-2 (HER2) receptor negative; and HER2 overexpressing: ER and PR negative but HER2 receptor positive. RESULTS: The number of patients in each group was 408 (68.5%), 105 (17.6%), and 83 (13.9%), respectively. The median follow-up period was 79 months. The TN and HER2 subtypes occurred in younger patients (p=0.0007) and had higher nuclear grade and poorer histologic grade (p<0.0001 and 0.0071, respectively). During the follow-up period, locoregional recurrence was detected as the first site of recurrence in 26 (6.4%), 11 (10.5%), and 9 (10.8%) patients in the luminal, TN, and HER2 subtypes, respectively (p=0.1924). Thirty-one (7.6%), 7 (6.7%), and 7 (8.4%) patients in each group had distant metastases as the first sign of recurrence (p=0.8996). Median time to locoregional and distant recurrence was shorter in the HER2 subtype (p=0.0889 and 0.0780, respectively), and the HER2 subtype was significantly associated with poor overall survival (p=0.0009). CONCLUSION: After BCT in Korean women with early stage breast cancer, the patterns of recurrence were not different among the molecular subtypes, although the TN and HER2 subtypes were associated with younger age, higher nuclear grade, and poorer histologic grade.

Implications of Bone-Only Metastases in Breast Cancer: Favorable Preference with Excellent Outcomes of Hormone Receptor Positive Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of the current study was to determine the incidence, clinical presentation, and treatment outcomes of "bone-only metastases" in patients with breast cancer and to analyze the impact of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status on prognosis. MATERIALS AND METHODS: Between 1994 and 2007, of 968 patients with metastatic breast cancer who underwent palliative management at Samsung Medical Center, 565 (57%) relapsed with distant metastases. Of the 968, 146 (15%) had bone-only metastases during a median follow-up period of 75 months. Among the 146 patients with bone-only metastases, 122 (84%) were relapsed patients after curative surgery and 24 (26%) were initially metastatic cases. RESULTS: The median time from primary surgery to bone-only metastases of the 122 patients was 37 months (95% confidence interval [CI], 27 to 46 months). Bone-only metastases were more common in the HR-positive group than in the other subtypes (85% for HR+; 8.2% for HER2+; 6.8% for triple negative. Among all 146 patients, 75 (51%) were treated with hormone therapy. The median post-relapse progression-free survival was 15 months (95%CI, 13 to 17 months). The median overall survival was much longer in the HR+ patients than the HER2+ and triple negative breast cancer patients with marginal statistical significance (65 vs. 40 vs. 40 months, p=0.077). CONCLUSION: Breast cancer patients with "bone-only metastases" had excellent clinical outcomes. Further study is now warranted to reveal the underlying biology that regulates the behavior of this indolent tumor, as it should identify 'favorable tumor characteristics' in addition to 'favorable preferential metastatic site.'

Inmunohistoquímica y expresión de receptores de estrógenos y progesterona en neoplasias mamarias malignas caninas en distintos estadios clínicos / Immunohistochemistry and expression of estrogen and progesterone receptors in canine malignant mammary tumors in different clinical stages

La técnica de inmunohistoquímica descrita por Walker y col. (1998) y Mote y col. (2001) es de utilidad para la determinación de receptores de estrógenos y de progesterona en tumores mamarios de la hembra canina. Existe bastante controversia respecto al porcentaje de receptores de estrógenos y de progesterona, con valor pronóstico o predictivo en tumores malignos caninos debido, muy probablemente, a la falta de uniformidad en criterios de inclusión de los casos en los estudios realizados. El presente trabajo se realizó en una población de 51 perras. Los tumores fueron escindidos quirúrgicamente mediante mastectomía de las glándulas afectadas. Para la determinación de receptores hormonales, se analizó la muestra con mayores características histológicas de malignidad de cada animal. Se contabilizó el porcentaje de células tumorales positivas para cada uno de los receptores (receptor de estrógeno alfa, receptor de estrógeno beta y receptores de progesterona) en los distintos estadios clínicos (I, II, II, IV). Se consideró positivo todo corte ³ 20% de células tumorales positivas para cada uno de los receptores. Se realizó una estadística descriptiva (media y error estándar) con los animales positivos para cada uno de los receptores en los distintos estadios clínicos. En línea con reportes de otros autores, más de la mitad de caninos portadores de tumores mamarios malignos expresaron receptores de estrógenos y de progesterona. Conociendo que el comportamiento biológico de una neoplasia varía con el estadio clínico del paciente, resulta interesante estudiar la expresión de los receptores en cada uno de éstos, en animales con neoplasias mamarias malignas. Adicionalmente, a este objetivo incluye la puesta a punto la de técnica de inmunohistoquímica para la determinación de receptores hormonales en la especie.

receptors in canine mammary tumors. There is considerable controversy regarding the percentage of estrogen and progesterone receptors that having prognostic or predictive value in malignant tumors in dogs because, most likely, the lack of uniform criteria for inclusion of cases. This study was conducted in a population of 51 female dogs. The tumors were surgically treated by mastectomy of the affected glands. For the determination of hormone receptors, the sample analyzed was showed higher histological malignancy features of each animal. It was counted the percentage of tumor cells positive for each of the receptors (estrogen receptor alpha, estrogen receptor beta and progesterone receptor) in animals in various clinical stages (I, II, III, IV). It was considered positive cut-off ³ 20% tumor cells positive for each of the recipients. It was conducted a descriptive statistics (mean and standard error) which positive animals for each of the receptors in different clinical stages. In line with reports of other authors, more than half of canine carriers of malignant mammary tumors expressed estrogen and progesterone receptors. Knowing that the biological behavior of cancer varies with the clinical stage of the animal, objective was to study the expression of receptors in each of the clinical stages in animals with malignant mammary tumors. Additionally, this includes the preparation of the immunohistochemical technique for the determination of hormone receptors in this species.

Estrogen and progesterone hormone receptor status in breast carcinoma: Comparison of immunocytochemistry and immunohistochemistry.

Context : Estrogen receptors (ER) and progesterone receptors (PR) play a significant role in the prognosis of breast cancer. For preoperative chemotherapy in locally advanced lesions, trucut biopsy is used to localize the ER and PR receptors by immunohistochemistry. Immunocytochemistry can be a better alternative to immunohistochemistry as it better fixes cells. AIMS : To evaluate the degree of correlation between immunocytochemical (ICC) and immunohistochemical (IHC) determination of ER and PR in breast cancer. Settings and Design : Fine needle aspiration cytology (FNAC) was performed on 100 primary breast cancers immunostained for ER and PR during a period of 1 year 7 months, i.e., from January 2006 to July 2007. Materials and Methods : Papanicolaou-stained slides were destained, fixed in cold acetone and submitted for immunocytochemistry. In the prospective analysis, FNAC smears were straightaway fixed in cold acetone and submitted for ER and PR. Peroxidase, antiperoxidase technique was used for immunocytochemistry. Statistical Analysis : Spearman Rank correlation test was used. Results : Differences between groups were analysed and correlations were studied. Concordance for ER was 50% and for PR was 29%. Both ER and PR were positive in four cases: ER only in three and PR in one, and both were negative in nine cases. Use of the least best buffer and technical errors contributed to the lower ICC rate. Conclusion : Although Immunocytochemistry removes the derogatory step of antigen deterioration, technical errors can cause hindrance in achieving the best of the results.