Integrated optical density analysis of the immunohistochemical expression of the progesterone receptor in the uterine endometrium of prepubertal araucana sheep / Análisis por densidad óptica integrada de la expresión inmunohistoquímica del receptor de progesterona en el endometrio uterino de ovejas prepúberes de raza araucana

SUMMARY: Progesterone receptors are expressed in the reproductive organs of adult sheep, where they regulate morphofunctional and reproductive development. However, various studies have shown the presence of these receptors in the uterus of prepubertal females. It is not clear what role these receptors have at this level of development in uterine tissue. Therefore, it is relevant as a first step in the investigation, to determine the expression and histological distribution of the progesterone receptor in prepubertal sheep in order to determine possible functions at this level of reproductive development. Immunohistochemical analysis allows visualizing the specific presence of a protein in the cellular and histological context, however, the results displayed through digital images are qualitative data and subject to the observer's criteria. In this work, a quantitative analysis method of immunohistochemical expression of the progesterone receptor in ovine endometrium is presented, using digital analysis of images, by means of integrated optical density of digital photographs of histological sections processed with immunohistochemical methods. The results show the possibility of quantitatively evaluating the expression of progesterone receptors in the endometrial stroma and prepubertal endometrial glands by applying the integrated optical density analysis of digital images.

RESUMEN: Los receptores de progesterona se expresan en los órganos reproductores de ovejas adultas, donde regulan el desarrollo morfofuncional y reproductivo. Sin embargo, diversos estudios han demostrado la presencia de estos receptores en útero de hembras prepúberes. No está claro, el papel que estos receptores tienen en este nivel de desarrollo en tejido uterino. Por lo que, es relevante como primer paso en la investigación, determinar la expresión y distribución histológica del receptor de progesterona en ovejas prepúberes con el fin determinar posibles funciones en este nivel de desarrollo reproductivo. El análisis inmuno- histoquímico permite visualizar la presencia específica de una proteína en el contexto celular e histológico, sin embargo, los resultados visualizados a través de imágenes digitales, son datos cualitativos y sujeto al criterio del observador. En este trabajo se presenta un método de análisis cuantitativo de expresión inmunohistoquímica del receptor de progesterona en endometrio ovino, utilizando análisis digital de imágenes, mediante densidad óptica integrada de fotografías digitales de cortes histológicos procesados con métodos inmunohistoquímicos. Los resultados muestran la posibilidad de evaluar cuantitativamente la expresión de los receptores de progesterona en el estroma endometrial y las glándulas endometriales prepúberes aplicando el análisis de densidad óptica integrado de imágenes digitales.

Association of menopausal status, expression of progesterone receptor and ki67 to the clinical response to neoadjuvant chemotherapy in luminal breast cancer / Associação de status menopausal, expressão de receptor de progesterona e de Ki67 à resposta clínica à quimioterapia neoadjuvante no câncer luminal de mama

Abstract Objective To identify the biomarkers of response to neoadjuvant chemotherapy in early luminal breast cancer. Methods A cross-sectional study that included all patients with early or locallyadvanced luminal breast cancer submitted to neoadjuvant chemotherapy between 2013 and 2014. Demographic, clinic and pathologic data were retrieved from patient records. The expressions of the estrogen receptor (ER), the progesterone receptor (PR), and Ki67 were analyzed by immunohistochemistry (IHC). The status of the human epidermal growth factor receptor 2 (HER2) was evaluated by IHC and fluorescent in situ hybridization (FISH). Independent predictors of clinic and pathologic response were evaluated by stepwise logistic regression models and receiver operating characteristic (ROC) curve analysis. Results Out of 298 patients identified, 115 were included in the analysis. Clinical complete response (cCR) was observed in 43.4% of the patients (49/113), and pathologic complete response (pCR) was observed in 7.1% (8/115) of the patients. The independent predictors of cCR were premenopausal status (p < 0.001), low PR expression (≤ 50% versus > 50%; p = 0.048), and Ki67 expression ≥ 14% (versus < 14%; p = 0.01). Patients with cCR were more commonly submitted to breast conserving surgery (34.7% versus 7.8%; p < 0.001). Increasing cut-off points for Ki67 expression were associated with an increase in specificity and a decrease in sensitivity to identify patients with cCR. Conclusion Premenopausal status, lower PR expression and higher Ki67 expression were associated with a higher rate of cCR to neoadjuvant chemotherapy in luminal breast cancer.

Resumo Objetivo Identificar biomarcadores de resposta à quimioterapia neoadjuvante em câncer luminal de mama. Métodos Estudo transversal em que foram incluídas todas as pacientes com câncer luminal de mama em estádio inicial ou localmente avançado que foram submetidas a quimioterapia neoadjuvante nos anos de 2013 e 2014. Dados demográficos, clínicos e patológicos foram obtidos de prontuários médicos. As expressões de receptor de estrogênio (RE), de receptor de progesterona (RP), e de Ki67 foram avaliadas por imuno-histoquímica (IHQ). A expressão do receptor tipo 2 do fator de crescimento epidérmico humano (human epidermal growth factor receptor 2, HER2) foi avaliada por IHQ e hibridização in situ por imunofluorescência (HISI). Análises de regressão logística e de curva de característica de operação do receptor (COR) foram usadas para investigar fatores preditivos independentes de resposta clínica e patológica. Resultados De 298 pacientes identificadas, 115 foram incluídas na análise. Resposta clínica completa (RCc) foi observada em 43.4% das pacientes (49/113), e resposta patológica completa (RPc), em 7.1% (8/115). Os fatores preditivos independentes de RCc foram status menopausal (p < 0.001), baixa expressão de RP (≤ 50% versus > 50%; p = 0.048), e expressão de Ki67 ≥ 14% (versus < 14%; p = 0.01). Pacientes com RCc apresentaram maior probabilidade de serem submetidas a cirurgia conservadora da mama (34.7% versus 7.8%; p < 0.001). Aumento no ponto de corte para expressão de Ki67 foi associado a aumento da especificidade e redução da sensibilidade na identificação de pacientes com RCc. Conclusão Status premenopausal, baixa expressão de RP e maior expressão de Ki67 estiveram associados a maior taxa de RCc à quimioterapia neoadjuvante no câncer luminal de mama.

Expression of estrogen and progesterone receptors in astrocytomas: a literature review

Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

Sonography of Invasive Apocrine Carcinoma of the Breast in Five Cases

OBJECTIVE: To evaluate the sonographic features of invasive apocrine carcinoma (IAC) of the breast. MATERIALS AND METHODS: This study included five pathologically proven cases of IAC, and their sonographic features were retrospectively analyzed according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon. RESULTS: All five lesions involved the left breast and were seen as irregularly shaped masses. All lesions, except one, had a parallel orientation to the chest wall. All five lesions showed noncircumscribed margins and heterogeneous echotexture; however, they showed various posterior features. One lesion had edema as an associated feature. Sonographic assessments were classified as BI-RADS category 4 in all five cases. CONCLUSION: Invasive apocrine carcinoma sonographic findings are difficult to differentiate from those of invasive ductal carcinoma of no special type.

ICON 2013: Practical consensus recommendations for hormone receptor-positive Her2-negative advanced or metastatic breast cancer.

The management of hormone receptor‑positive Her2‑negative breast cancer patients with advanced or metastatic disease is a common problem in India and other countries in this region. This expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

Conservative therapy with metformin plus megestrol acetate for endometrial atypical hyperplasia / 부인종양

OBJECTIVE: To compare the efficacy of metformin plus megestrol acetate (MA) with that of MA alone for treating endometrial atypical hyperplasia (EAH). METHODS: This pilot study included 16 EAH patients who met at least one metabolic syndrome (MS) criterion and received either adjunctive metformin plus MA (MET group) or MA monotherapy (MA group). Each patient in the MA group received 160 mg of MA daily, whereas patients in the MET group received the same dose of MA plus 0.5 g of metformin thrice daily. Treatment response was assessed by histological examination of dilation and curettage specimens obtained after 12 weeks of therapy. RESULTS: Each group had eight patients, and half of the patients in each group were diagnosed with MS. The complete response (CR) rate was 75% (6/8) in the MET group and 25% (2/8) in the MA group (p=0.105). Complications of MS did not affect the response rates in either group. In the MET group, 75% (3/4) of the patients had CR in the presence or absence of MS. In the MA group, 50% (2/4) of the patients with MS had CR, whereas no patient without MS had CR. No irreversible toxicities were observed. CONCLUSION: Metformin plus MA may be a potential alternative therapy for treating EAH, and the MS status of patients may have no effect on the efficacy of metformin plus MA therapy.

Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease. .

Terapia endocrina neoadyuvante en cáncer de mama, una alternativa de tratamiento e investigación / Neoadyuvant endocrine therapy in breast cancer

Neoadjuvant chemotherapy is an accepted strategyforpatients with locally advanced breast cáncer. This approach increases the possibilities ofconservative treatment and improves the resectability rates ofinitially unresectable tumors. In addition, preoperative systemic therapy allows the evaluation of prognostic and predictive factors, dynamically and in vivo. Since over 80% ofthese tumors express estrogen receptors (ER), endocrine therapy seems a logical treatment to employ in the neoadjuvant setting. The advent ofnew drugs that regúlate the ERfunction, along with the results of severa! clinical studies with the use of neoadjuvant endocrine therapy, support the feasibility and safety of utilizing this strategy before surgery. We herein analyze the available clinical evidence about the use of neoadjuvant therapy aiming to regúlate the activity ofthe ER. We also discuss the valué of predictive factors that could help the oncologist to select those patients most likely to benefit from this approach and the role of endocrine therapy as a research instrument.

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.

Immunophenotypes of Glycogen Rich Clear Cell Carcinoma

PURPOSE: Glycogen rich clear cell carcinoma (GRCC) of the breast is a rare subtype of invasive ductal carcinoma and involves a poor prognosis. In the literature, less than 150 cases have been reported. Many researchers have attempted to characterize GRCC according to electron microscope, flow cytometry, or clinical data. However, an organized study of the immunophenotype of GRCC has yet to be reported. MATERIALS AND METHODS: Here, we present three cases of GRCC and their immunohistochemical profiles. RESULTS: Histologically, all three cases contained periodic acid stain (PAS) positive and d-PAS labile granules in their clear cytoplasm. Case I showed positivity for only estrogen receptor (ER) and c-erbB2. Case II exhibited positivity for progesterone receptor and negativity for ER and c-erbB2. Case III presented with triple negative invasive carcinoma. The expression pattern of E-cadherin was concordant with epidermal growth factor receptor and c-kit, but discordant with ki-67. Among these three cases, p53-positive cases exhibited a low proliferative index (ki-67: 15%), while p53-negative cases showed a high proliferative index (ki-67: 50-60%). CONCLUSION: In conclusion, the immunophenotype of GRCC is not uniform, but is similar to that of conventional ductal carcinoma.

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.

Moduladores seletivos dos receptores da progesterona: revisão da literatura / Selective modulators of progesterone receptors: literature review

Os moduladores seletivos dos receptores da progesterona (MSRP) são substâncias sintéticas derivadas dos esteroides que têm a capacidade de ocupar os receptores da progesterona e passam a ter ação como antagonista, agonista-antagonista ou agonista desse hormônio, dependendo do tecido alvo. Essas variedades de ações favorecem a utilização dessas substâncias para o tratamento da miomatose uterina, endometriose, entre outros, tendo também importante aplicação na anticoncepção e na reprodução assistida. O mecanismo de ação dos MSRP não está completamente elucidado, uma vez que intercalam efeitos sinérgicos e antagônicos aos da progesterona. Entretanto, sabe-se que têm efeito antiproliferativo, antiangiogênico, aumentam os índices de apoptose celular e promovem uma diminuição do aporte sanguíneo das artérias uterinas e dos vasos espiralados do endométrio. O tempo de utilização dessas drogas é restrito devido aos seus efeitos adversos relacionados, principalmente, alterações endometriais, propriedades abortivas de alguns compostos e efeitos adversos associados com a dose e a utilização em longo prazo.

The selective modulators of progesterone receptors (MSRP) are synthetic compounds derived from steroids that have the ability to bind the progesterone receptor. These substances can act as an antagonist, agonist-antagonist or agonist of the progesterone, and these effects are specific for each target tissue. These properties favor the use of these substances for the treatment of uterine fibroids and endometriosis. These componds can also be used in assisted reproduction and contraception. The precise mechanism by which MSRP acts is not fully understood. However, it is known that these componds have antiproliferative and antiangiogenic effects. Also, MSRP promotes an increase in the rates of apoptosis and decreased blood supply of uterine arteries and vessels of the endometrium. The time of use of these drugs is restricted due to its adverse effects mainly related to endometrial changes, its abortion properties, and adverse effects associated with dose and long-term use.

A long-term survival pattern for breast cancer treated in a single institution.

Aim: This paper presents a 14-year retrospective study evaluating the survival rates and prognostic factors of breast carcinoma patients treated in private treatment center in the west coast of Turkey. Materials and Methods: The survival rates of breast cancer patients (n = 1746) who have been treated from 1995 until 2008 were analyzed. The clinical data include age, menopausal stage, oestrogen (ER) and progesterone (PR) receptor status, and C-erbB-2 status as well as histopathological evaluation. AJCC (2002) was used for clinical tumor staging. Survival rates were computed using standard Kaplan-Meier methods, and the difference in survival curves was analyzed with the log-rank test. Results: The 14-year overall survival, disease-free survival, local failure-free survival, and distant failure-free survival rates were 77%, 95%, 77%, and 94%, respectively. Early-stage patients had higher overall survival rates compared to advanced-stage patients (stage IIIb and IIIc, AJCC 2002), and early-stage patients had higher survival rates than advanced-stage patients for disease-free survival, local failure-free survival, and distant failure-free survival. The risk for cancer development increases significantly for advanced-stage patients with positive ER and PR receptor as well as C-erbB-2 receptor. Conclusions: The incidence of breast cancer in Turkey is smaller compared to other European countries. Low advanced-stage patient numbers compared to high early-stage patient numbers; and very high median survival times could possibly be the result of the improvement of detection and treatment of breast cancer over the years.

Transcriptional regulation of bidirectional gene pairs by 17-β-estradiol in MCF-7 breast cancer cells

Using cDNA microarray analysis, we previously identified a set of differentially expressed genes in primary breast tumors based on the status of estrogen and progesterone receptors. In the present study, we performed an integrated computer-assisted and manual search of potential estrogen response element (ERE) binding sites in the promoter region of these genes to characterize their potential to be regulated by estrogen receptors (ER). Publicly available databases were used to annotate the position of these genes in the genome and to extract a 5’flanking region 2 kb upstream to 2 kb downstream of the transcription start site for transcription binding site analysis. The search for EREs and other binding sites was performed using several publicly available programs. Overall, approximately 40 percent of the genes analyzed were potentially able to be regulated by estrogen via ER. In addition, 17 percent of these genes are located very close to other genes organized in a head-to-head orientation with less than 1.0 kb between their transcript units, sharing a bidirectional promoter, and could be classified as bidirectional gene pairs. Using quantitative real-time PCR, we further investigated the effects of 17β-estradiol and antiestrogens on the expression of the bidirectional gene pairs in MCF-7 breast cancer cells. Our results showed that some of these gene pairs, such as TXNDC9/EIF5B, GALNS/TRAPPC2L, and SERINC1/PKIB, are modulated by 17β-estradiol via ER in MCF-7 breast cancer cells. Here, we also characterize the promoter region of potential ER-regulated genes and provide new information on the transcriptional regulation of bidirectional gene pairs.

Expression of Hypoxia-inducible factor 1-α and Vascular endothelial growth factor-C in locally advanced breast cancer patients

BACKGROUND: Locally advanced breast cancers are more prevalent in underdeveloped countries. Targeted therapy has been improved to identify hallmarks that are specific to these subtypes of tumors. OBJECTIVES: We aimed to prospectively assess the expression of Hypoxia inducible factor-1 α and vascular endothelial growth factor-C in locally advanced breast cancer patients. METHODS: Thirty women underwent incisional biopsies for the histopathological diagnosis of breast carcinoma and participated in neoadjuvant chemotherapy. The association of Hypoxia inducible factor-1 α and vascular endothelial growth factor-C with age, tumor size, histological grade, clinical staging, hormonal and axillary status, clinical and pathological response after neoadjuvant chemotherapy, expression of estrogen and progesterone receptors, and the presence of c-erbB-2 antigen was studied. RESULTS: Hypoxia inducible factor-1 α expression and Vascular endothelial growth factor-C expression were observed in 66.7 percent and 63.3 percent of all patients, respectively, and were marginally associated with each other (p = 0.06). Among the studied variables, only positive axillary status was associated with the presence of HIF-1α (p = 0.02). Complete pathological response was significantly associated (p = 0.04) with the expression of vascular endothelial growth factor-C prior to neoadjuvant chemotherapy. CONCLUSION: We concluded that Hypoxia inducible factor-1 α was associated with a poor prognosis and that vascular endothelial growth factor-C could be used as a predictive factor in locally advanced breast cancer patients with complete pathological response after neoadjuvant chemotherapy.

Clinicopathlogic and Immunohistochemical Characteristics of Triple Negative Invasive Lobular Carcinoma

PURPOSE: Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts. MATERIALS AND METHODS: Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC. RESULTS: Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs. CONCLUSION: TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.

Refractory Hypertension and Isosexual Pseudoprecocious Puberty Associated with Renin-Secreting Ovarian Steroid Cell Tumor in a Girl

Steroid cell tumor, not otherwise specified (NOS), are rare ovarian tumor, in addition, it is more rare in children. The majority of these tumors produce several steroid hormones, particularly testosterone. Estrogen also secreted by steroid cell tumor, NOS, but it is uncommon. Furthermore, hypertension is an infrequent sign in steroid cell tumor, NOS. An 8.5-yr-old girl with hypertension and frequent vaginal spotting visited at our clinic. On laboratory evaluation, secondary hypertension due to an elevated plasma renin level and isosexual pseudoprecocious puberty was diagnosed. Right solid ovarian mass was detected in radiologic tests. She underwent a right ooporectomy and it revealed renin and progesterone receptor positive steroid cell tumor, NOS. After operation, her blood pressure returned to normal level and vaginal bleeding disappeared. Even though this case is very rare, when hypertension coincides with virilization or feminization, a renin-secreting ovarian steroid cell tumor, NOS, should be considered.

Evaluation of the estrogenic effects of dietary perinatal Trifolium pratense

This study was designed to investigate the potential estrogenic effects of perinatal dietary phytoestrogens on the rat uterus. Pregnant rats were divided to three groups provided the following diets: (1) rat chow, (2) rat chow with 7.5% Trifolium (T.) pratense, or (3) rat chow supplemented with 17beta-estradiol (0.5 mg/kg). The dams in each group were kept on the same diet during pregnancy and lactation. Female offspring were euthanized on day 21 at which time body and organ weights were recorded and tissue samples were taken for histology. Immunohistochemistry was performed to detect estrogen receptor alpha (ERalpha) and progesterone receptor (PR) levels. Our results revealed estrogen-like biological effects of perinatal T. pratense exposure. Relative uterus and ovary weights in the experimental groups were increased compared to control. The number of uterine glands and luminal epithelium heights were also increased. However, there were no statistically significant changes detected in the immunostaining intensity of ERalpha and PR between the groups.

Immunohistochemical expression of oestrogen and progesterone receptors during experimental acute and chronic murine Schistosomiasis mansoni / Expressão imunohistoquímica de receptores para estrogênio e progesterona nas fases aguda e crônica da esquistossomose mansônica experimental em camundongos

INTRODUCTION: The responsibility of Schistosoma mansoni in female infertility is still controversial. This study was conducted to evaluate the effect of acute and chronic schistosomiasis mansoni infection on the endometrium using immunohistochemical analysis of uterine hormone receptor expression. METHODS: Twenty-four nonpregnant swiss albino mice were divided into three groups: control, noninfected; acute; and chronic Schistosoma mansoni infection. Histological sections of uterine specimens were examined by light microscope with an image analyzing system to detect structural histological, estrogen receptor (ER) and progesterone receptor (PR) expression in the endometrium. RESULTS: No secretory phase was detected in the endometrium in acute and chronic Schistosoma infection. Hormone receptor expression (ER and PR) showed statistically significant differences among the groups (p< 0.05), with significant low ER hormone expression in chronic infection, compared to control proliferative, control secretory and acute infection cases, and statistically significant high PR expression in both acute and chronic infection cases compared to the control secretory cases (p< 0.05). CONCLUSIONS: Schistosomiasis mansoni seems to have an important impact on the hormone expression of affected women. Further studies to explore the mechanism of such changes are recommended.

INTRODUÇÃO: A responsabilidade do Schistosoma mansoni em esterilidade feminina é ainda controversa. Este estudo é conduzido para avaliar o efeito da esquistossomose mansoni aguda e crônica no endométrio usando análise de imuno-histoquímíca da expressão de receptor hormonal uterina. MÉTODOS: Vinte e quatro camundongos fêmeas albinas suíças não grávidas foram divididas em 3 grupos (controle não-infectado, grupos agudos e crônicos infeccionados com Schistosoma mansoni). As seções histológicas de espécimes uterinos foram examinadas por microscópio leve com imagem, analisando sistema para detectar no endométrio expressões histológicas estruturais, receptor de estrogênio (ER) e receptor de progesterona (PR). RESULTADOS: Nenhuma fase secretora foi detectada no endométrio com infecção aguda e crônica de Schistosoma. A expressão hormonal de receptor (ER e PR) mostrou diferenças estatisticamente significantes entre grupos diferentes (p<0,05) com baixa significativa hormonal de ER com infecção crônica (comparado com controle proliferativo, controle secretório e casos agudos de infecção) e alta expressão de receptor de PR estatisticamente significativa em casos tanto agudos e crônicos de infecção como comparado com os casos de controle secretório (P <0,05). CONCLUSÕES: A esquistossomose mansoni parece ter um maior impacto em expressão hormonal das mulheres afetadas. Mais estudos para explorar o mecanismo de tais mudanças são recomendados.