Estrogen receptor mRNA determined by Quantitative Real-Time PCR in the nasal mucosa of women taking oral contraceptives / Receptor ARNm de estrógeno determinado por PCR Cuantitativa en Tiempo Real en la mucosa nasal de mujeres tratadas con anticonceptivos orales

SUMMARY: Estrogen receptors (ER) have been identified in human nasal mucosa, but its physiologic and pathologic impacts are not totally established. ER have been demonstrated in nasal mucosa by several authors, mainly by immunohistochemical method in nasal mucosa samples surgically removed. The present study aimed to quantify ERα and ERβ mRNA concentration by using an absolute quantitative real-time PCR in cells from nasal mucosa smear of women under oral contraceptive therapy. Nasal epithelium smear samples were collected from 110 patients divided in two groups: 55 women who present regular menstrual cycle without using contraceptives and 55 women who present regular menstrual cycle and have been using oral contraceptives for more than 3 months. All the patients answered a rhinitis symptoms questionnaire. The current study showed the potential usefulness of nasal turbinate mucosa cell sourcing, collected through swab, for extracting useful RNA for gene expression. We have identified the predominant expression of ERα isoform in a ratio 10-15 times higher compared to ERβ isoform. There is a tendency for positive correlation between the ERb isoform and the rhinitis severity score.

RESUMEN: Se han identificado receptores de estrógeno (RE) en la mucosa nasal humana, sin embargo sus impactos fisiológicos y patológicos aún no están totalmente establecidos. Varios autores han demostrado RE en la mucosa nasal, principalmente por método inmunohistoquímico en muestras obtenidas quirúrgicamente. El presente estudio tuvo como objetivo cuantificar la concentración de ARNm de REa y REb mediante el uso de una PCR cuantitativa absoluta en tiempo real en células de frotis de mucosa nasal de mujeres bajo terapia anticonceptiva oral. Se recolectaron muestras de frotis de epitelio nasal de 110 pacientes divididas en dos grupos: 55 mujeres que presentan ciclo menstrual regular sin uso de anticonceptivos y 55 mujeres que presentan ciclo menstrual regular con uso de anticonceptivos orales durante más de 3 meses. Todas las pacientes respondieron un cuestionario de síntomas de rinitis. El estudio actual mostró la utilidad de la obtención de células de la mucosa de la concha nasal, recolectadas a través de un hisopo, para extraer ARN para la expresión génica. Hemos identificado la expresión predominante de la isoforma REμ en una proporción de 10 a 15 veces mayor en comparación con la isoforma REß. Hemos identificado la expresión predominante de la isoforma REα en una proporción de 10 a 15 veces mayor en comparación con la isoforma REß. Existe una tendencia a una correlación positiva entre la isoforma REß y la puntuación de gravedad de la rinitis.

Hormone receptor-negative as a predictive factor for pathologic complete response to neoadjuvant therapy in breast cancer / Receptor hormonal negativo como fator preditivo para resposta patológica completa ao tratamento neoadjuvante de câncer de mama

ABSTRACT Objective To define a predictive factor for pathologic complete response, compare the oncologic outcomes associated with the degree of pathologic response after neoadjuvant chemotherapy, and to analyze pathologic complete response as a prognostic factor for overall survival and progression-free survival. Methods A retrospective study of patients admitted to Hospital Estadual Mário Covas and Hospital Anchieta from 2008 to 2012, with locally advanced breast cancer. Hormone receptor status, HER2 status, histologic and nuclear grade, age upon diagnosis and histological type of the tumor were analyzed. Pathologic evaluation of the tumor was subdivided into pathologic complete response, defined by the absence of tumor; intermediate response, considered as a favorable stage; and poor response, considering low-responder patients. Data obtained were submitted to statistical analysis. Results The study included 243 patients. There was an association of pathologic complete response with HER-2 negative, histological grade 3, stage III, hormone receptor negative, positive lymph node, older age and more advanced tumors. However, after multivariate analysis the only predictor of pathologic complete response was the presence of negative hormone receptor. By analyzing the prognostic factors, hormone receptor negative was considered as an independent risk factor, and pathologic complete response was considered as an independent protective factor. Conclusion Hormone receptor negative is predictive of pathologic complete response and is an isolated risk factor for lower progression-free survival and overall survival. Pathologic complete response is a protective factor for these same survival analyses.

RESUMO Objetivo Definir um fator preditivo para resposta patológica completa, comparar os resultados oncológicos associados com o grau de resposta patológica, após quimioterapia neoadjuvante, e analisar a resposta patológica completa como fator prognóstico para sobrevivência global e livre de progressão de doença. Métodos Estudo retrospectivo de pacientes admitidas no Hospital Estadual Mário Covas e Hospital Anchieta, no período de 2008 a 2012, com câncer de mama localmente avançado. Foram utilizados status dos receptores hormonais, proteína HER2, grau histológico e nuclear, idade do paciente ao diagnóstico e tipo histológico do tumor. A avaliação patológica do tumor foi subdividida em resposta patológica completa, definida com ausência de tumor; resposta intermediária, considerada como um estádio favorável; e resposta ruim, considerando os pacientes pouco respondedores. As informações obtidas foram submetidas à análise estatística. Resultados Foram incluídas 243 pacientes. Verificou-se associação de resposta patológica completa entre HER-2 negativo, grau histológico 3, estadiamento III, receptor hormonal negativo, linfonodo positivo, maior idade e tumores mais avançados. Porém, após análise multivariada, o único fator preditivo de resposta patológica completa foi presença de receptor hormonal negativo. Ao analisar fatores prognósticos, receptor hormonal negativo permaneceu como variável independente de risco, e resposta patológica completa, como variável independente de proteção. Conclusão O receptor hormonal negativo é fator preditivo isolado de resposta patológica completa e fator de risco para menor sobrevida livre de doença e sobrevida global. Já a resposta patológica completa é fator protetor para estas mesmas análises de sobrevivência.

Clinicopathological analysis of aggressive angiomyxoma of soft tissue in abdomino-pelvic cavity / 北京大学学报(医学版)

Aggressive angiomyxoma is a rare mesenchymal tumor. To discuss the clinicopathological characteristics, treatment and prognosis of aggressive angiomyxoma, four cases of aggressive angiomyxoma of soft tissue in abdominopelvic cavity were collected from January 2015 to August 2017 in Peking University International Hospital. The clinical data, imaging examination, histopathological features, immunophenotype, therapy and prognosis were analysed. The related literatures were reviewed. All of the patients were adult females, age range from 27 to 49 years and mean 33 years. The clinical complaint was abdominal distention with no definite predisposing factor, or occasional physical-exam finding with no obvious discomfort. Three cases were primary and one case was recurrent. Typical layered or swirled structural sign was presented by CT and MRI scanning of three cases. All tumors located in the pelvic cavity, and attached to the uterus, vagina, rectum, bladder or ureter. One case was involved in the abdominal cavity simultaneously,adhesive to the spine, inferior vena cava and spleen. The gross appearance of tumors was from 5 to 22 cm in maximum diameter. The sectioned surfaces were soft, solid, white or yellow-gray, focally accompanied by edema, mucoid degeneration or cystic change. Microscopic observation showed that tumor cells were short spindle shaped and little atypical, the stroma was loose like edematous mucus or collagen, and the vessels were rich in thin and thick-wall. Partially the vessel wall expressed hyaline degeneration. Also tumors might infiltrate surrounding tissue, such as fat or nerve. The immunohistochemistry results of all cases were estrogen receptor and progesterone receptor diffusely moderate positive, Desmin and smooth muscle actin mostly positive, whereas CD34 expressed only in vessel and S-100 protein, CD117 and Dog1 all negative. All the tumors were complete surgical excision. During follow-up, one case recurred the second time. Our conclusions are the diagnosis of aggressive angiomyxoma is based on pathological morphology supplemented by immunohistochemistry, and the tumor may relapse after surgical resection.

Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes

OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

Worse prognosis in breast cancer patients can be predicted by immunohistochemical analysis of positive MMP-2 and negative estrogen and progesterone receptors / Pacientes com câncer de mama de pior prognóstico podem ser estimadas por análise imuno-histoquímica de MMP-2 positiva e receptores de estrógeno e progesterona negativos

Summary Introduction: Breast cancer is the most cause of death, and approximately 90% of these deaths are due to metastases. Matrix metalloproteinase-2 (MMP-2) gelatinase activity is able to degrade a major constituent of the tumor microenvironment, type IV collagen. Two well-established proteins used as markers in clinical practice for breast cancer are the receptors for estrogen (ER) and progesterone (PR). Although the presence of these receptors has been associated with a better prognosis, loss of these proteins can occur during tumor progression, with subsequent resistance to hormone therapy. Objective: To study the correlation among MMP-2, ER, and PR, as well as the establishment of the metastatic process in primary breast tumors. Method: Breast cancer samples (n=44) were analyzed by immunohistochemistry for MMP-2, ER, and PR. Results: We observed that 90% of patients who had metastases and died showed positive staining for MMP-2 (p=0.0082 for both). Using Kaplan-Meier analysis, we found that negative ER patients who were also positive for MMP-2 had even worse disease-free survival (DFS) and overall survival (OS) (p= 0.012 and p=0.005, respectively). Similar results were found in PR-negative patients for DFS (a trend p=0.077) and OS (p=0.038). Conclusion: Regardless of our small sample size (n=44), the data obtained strongly suggest that MMP-2 in combination with already well-established markers could help to predict the emergence of metastases and death in patients with breast cancer.

Resumo Introdução: o câncer de mama é a segunda causa de morte no mundo, sendo 90% dessas mortes decorrentes de metástases. A metaloprotease de matriz 2 (MMP-2) possui atividade de gelatinase capaz de degradar o principal constituinte do microambiente tumoral, o colágeno do tipo IV. Há duas proteínas bem estabelecidas utilizadas como marcadores na prática clínica para o câncer de mama, os receptores de estrógeno (RE) e de progesterona (RP). Embora a presença desses receptores tenha sido associada a um melhor prognóstico, a perda delas pode ocorrer durante a progressão do tumor, com subsequente resistência à terapia hormonal. Objetivo: analisar a correlação entre as proteínas MMP-2, RE e RP por imuno-histoquímica e estabelecer o processo metastático em tumores de mama primários. Método: amostras de tumor de mama (n=44) foram analisadas por imuno-histoquímica para MMP-2, receptor de estrógeno e progesterona. Resultados: observou-se que 90% das pacientes que tinham metástases e morreram apresentaram coloração positiva para a MMP-2 (p=0,0082 para ambos). Usando a análise de Kaplan-Meier, verificou-se que as pacientes RE negativas, também positivas para MMP-2, apresentaram sobrevida livre de doença (SLD) e sobrevida global (SG) (p=0,012 e p=0,005, respectivamente) piores quando comparadas às pacientes MMP-2 negativas. Resultados semelhantes foram encontrados em pacientes RP negativas para SLD (p=0,077) e SG (p=0,038). Conclusão: embora o número de amostras avaliadas tenha sido baixo (n=44), esses dados iniciais permitem inferir que a MMP-2 em combinação com os marcadores já bem estabelecidos poderia ajudar na previsão do surgimento de metástase e morte em pacientes com câncer de mama.

Increased Expression of Forkhead Box M1 Is Associated with Aggressive Phenotype and Poor Prognosis in Estrogen Receptor-Positive Breast Cancer

Fox transcription factors play a critical role in the regulation of a variety of biological processes. While FoxM1 behaves like the oncogenic transcription factor, FoxO3a is known as a tumor suppressor by inhibiting FoxM1. This study aimed to investigate the clinicopathological significance of FoxM1 and FoxO3a expression in breast cancer. Expression of FoxM1 and FoxO3a were analyzed by immunohistochemical staining on tissue microarray sections from 236 breast cancer patients, and correlated with various clinicopathological characteristics. Overexpression of FoxM1 correlated with adverse clinicopathological features, such as larger tumor size, lymph node metastasis, advanced tumor stage, and lymphovascular invasion. The Kaplan-Meier survival curves revealed no prognostic significance of FoxM1 expression. However, in subgroup analyses with patients of estrogen receptor (ER) positive breast cancers, FoxM1 overexpression associated with poor disease free and overall survival. No association was found between FoxO3a and FoxM1 expression. Regarding clinicopathological variables, the only association between histologic grade and FoxO3a was observed. In conclusion, FoxM1 overexpression was significantly associated with aggressive phenotypes and poor prognosis of ER-positive breast cancer. These findings suggest the possible role of FoxM1 as a prognostic biomarker and putative target of anti-cancer therapy.

Triple-negative breast cancer that progressed as estrogen receptor-positive skin metastases

No abstract available.

Cáncer de mama metastásico: Caracterización de una cohorte según subtipos / Survival of patients with metastatic breast cancer according to pathological types of tumors

Background: The prognosis of breast cancer (BC) is in part determined by the stage at diagnosis and its pathological characteristics. Aim: To evaluate the association between survival of women with metastatic breast cancer and pathological features of the tumor. Patients and Methods: We obtained clinical and pathological data from patients diagnosed with a metastatic BC between 1999 and 2013. The expression of estrogen (ER) and progesterone (PR) receptors and human epidermal growth factor receptor 2 (HER2) was determined by immunohistochemistry. Clinicopathological subtypes were defined as: Luminal A: ER or PR positive, HER2 negative, histological grade (HG) 1 or 2; Luminal B: ER or PR positive, HER2 negative or positive or HG 3; triple negative (TN): ER, PR and HER2 negative, independent of the HG, positive HER2: ER, PR negative and HER2 positive, independent of HG. We analyzed survival based on these subtypes. Results: We identified 54 patients aged 24 to 85 years, with metastatic BC at diagnosis. Seventy five percent had luminal tumors; 19.6% HER2 positive and 7.8% were TN. In 61% of evaluable tumors, HG was classified as 3. The frequency of HER2 positive and high HG tumors was greater in these patients with metastatic BC than in a non-metastatic local BC cohort. Survival was higher among patients with Luminal tumors than in women with non-Luminal cancer (56.4 and 11.4 months, respectively, p = 0.04). Conclusions: Patients with metastatic BC at diagnosis often had HER2 positive tumors and high HG. As in other studies, ER positive tumors had a better survival.

Histological investigation of the effect of soybean (Glycine max) extracts on the collagen layer and estrogen receptors in the skin of female rats

OBJECTIVES: The purpose of this study was to analyze the effects of soybean extracts obtained using different extraction methods on the skin of female rats. METHOD: A total of 64 female Sprague-Dawley rats were divided into 8 equal groups. Various extracts were administered to the female rats by oral gavage for one month. The groups comprised carboxymethyl cellulose-free control, carboxymethyl cellulose-plus control, 100-mg/kg n-hexane extract, 200-mg/kg n-hexane extract, 100-mg/kg ethyl acetate extract, 200-mg/kg ethyl acetate extract, 100-mg/kg ethanol extract and 200-mg/kg ethanol extract groups. The thickness of the collagen layer and the number of estrogen receptor-positive cells were evaluated. RESULTS: All the extract-treated groups showed a statistically significant decrease in the number of estrogen receptor-positive cells compared with the control groups. Regarding the thickness of the collagen layer, only the 200-mg/kg ethyl acetate extract-treated group showed a significant increase compared with the control groups (p<0.05). CONCLUSIONS: Our data suggest that oral intake of three different total soybean extracts might have positive estrogenic effects on the skin and that only a high-dose ethyl acetate extract can increase the expression of collagen, which may prove to be beneficial for postmenopausal facial skin. ...

Expression of procaspase 3 and activated caspase 3 and its relevance in hormone-responsive gallbladder carcinoma chemotherapy

BACKGROUND/AIMS: The higher incidence of gallbladder cancer (GBC) in females has been accredited to the involvement of hormones. The clinical implications of sex hormone receptors in GBC are well established. Cysteine proteases (such as caspase-3-9, etc.) are known to play a central role in the apoptotic pathway. Of these, the downstream enzyme caspase-3 is often activated in the apoptotic pathway. The aim of this work was to examine the status of apoptosis (which directly correlated with the level of active caspase-3) in hormone-responsive GBC. METHODS: We used 10 androgen receptor (AR)-positive, 14 estrogen receptor (ER)-positive, 12 HER/neu-positive, eight triple positive, and 10 triple negative malignant GBC human tissue samples. We isolated the total cellular protein from tumor tissues and carried out Western blotting using antipro-caspase-3 and anti-activated caspase-3 antibodies. RESULTS: ER and HER/neu-positive GBC exhibited high caspase-3 activity and low procaspase-3 activity, whereas AR-positive GBC showed no significant level of apoptosis. We also evaluated the apoptosis status of triple positive GBC and triple negative GBC, and found significant apoptosis in triple positive GBC. CONCLUSIONS: The results indicate that ER and HER/neu-positive GBCs had active apoptosis, whereas AR-positive GBC was highly resistant to apoptosis.

Expressão gênica dos REα, REβ e PR em tumores mamários de cadelas por meio do q-PCR / REα, REβ and PR gene expression in mammary gland tumors of female dogs by q-PCR

A expressão de receptores de estrógeno (ER) e progesterona (PR) por meio da técnica de q-PCR foi avaliada em 26 cadelas portadoras de neoplasias mamárias e cinco cadelas sem afecções mamárias (grupo controle). Os resultados mostraram que os três grupos de animais estudados - com tumor maligno ou benigno e controle - expressaram receptores de estrógeno alfa, beta e progesterona. A quantificação relativa mostrou tendência para uma expressão maior de receptores no grupo controle e menor no grupo de animais com neoplasias malignas. Além disso, observou-se expressão maior de ERα em relação ao ERβ, e as neoplasias malignas de origem mista apresentaram maiores concentrações dos receptores PR, ERα e ERβ que as neoplasias de origem epitelial.

The estrogen and progesterone receptor (ER and PR) expression with the q-PCR technique was evaluated in 26 female dog carrying of mammary tumors and five female dogs without mammary disease (control group). The results showed that the three animal groups evaluated - malignant or benign tumor and control - expressed alpha and beta estrogen and progesterone receptors. The relative quantification showed a tendency for a higher expression of receptors from the control group and smaller in the malignat tumors animal group. Also, there was a major ERα expression regarding to ERβ and the malignat tumors from mixed origin presented higher concentrations of receptors PR, ERα and ERβ, when compared to tumors of epithelial origin.

Detección inmunohistoquímica del receptor de estrógeno en el endometrio de ovejas de alta prolificidad y de prolificidad estándar / Immunohistochemical detection of estrogen receptor in the endometrium of sheep high prolificacy and standard prolificacy

Uno de los factores que incide en la capacidad reproductiva de los ovinos es la presencia de receptores de estrógeno en el tracto genital, donde regulan la expresión de numerosos genes comprometidos en su desarrollo morfológico y funcional. Posiblemente el desempeño reproductivo de diferentes razas de ovejas podría estar determinado por la expresión diferencial de estos receptores. En el presente estudio, se evaluó comparativamente el nivel de expresión del receptor de estrógeno en tejido endometrial de ovejas prepúberes de alta prolificidad (raza Texel) y de prolificidad estándar (raza Araucana) mediante análisis inmunohistoquímico. Se concluye que el nivel de expresión del receptor de estrógeno en tejido estromal, epitelial, de revestimiento y glandular del endometrio de ovejas de raza Texel es significativamente mayor que en ovejas de raza Araucana. Esta diferencia en el nivel de expresión de estos receptores podría estar relacionado con la diferencia de prolificidad entre estas razas...

A factor that affects the reproductive capacity of sheep is the presence of estrogen receptors in the genital tract, where they regulate the expression of numerous genes involved in morphological and functional development. Possibly the reproductive performance of different breeds of sheep could be determined by the differential expression of these receptors. In the present study, we evaluated comparatively level of estrogen receptor expression in endometrial tissue ewe lambs high prolificacy (Texel) and standard prolificacy (Araucana) by immunohistochemical analysis. It is concluded that the level of estrogen receptor expression in stromal tissue, epithelial lining and endometrial glandular Texel Sheep is of greater intensity than in ewes Araucana, this difference in the expression level of these receptors could be related to the increased prolificacy of Texel breed...

Molecular mapping of heterocyclic diazene derivatives for estrogen receptor modulation.

Selective estrogen receptor modulators (SERMs) are effectively used in hormone replacement therapy (HRT) by reducing post-menopausal symptoms, including hormone-responsive breast cancer and osteoporosis. The present study explored the pharmacophore features of diazene derivatives for selective estrogen receptor (ER) modulation using quantitative structure activity relationship (QSAR) and space modeling approaches. The 2D-QSAR models (R2α = 0.907, Q2α = 0.700, R2pred-α = 0.735; R2β = 0.913, Q2β = 0.756, R2pred-β = 0.745) showed the importance of orbital energies, hydrophobicity, refractivity and atomic charges for selective binding affinity to ER. In 3D-QSAR, molecular field (CoMFA, R2α = 0.948, Q2 = 0.720, R2pred-α = 0.708; R2β = 0.994, Q2β = 0.541, R2pred-β = 0.721) and similarity models (CoMSIA, R2α = 0.984, Q2α = 0.793, R2pred-α = 0.738; R2β = 0.996, Q2β = 0.681, R2pred-β = 0.725) indicated that steric and hydrophobic properties were important for binding selectivity. Space modeling study (R2α = 0.885, Q2α = 0.855, R2pred-α = 0.666; R2β = 0.872, Q2β = 0.883, R2pred-β = 0.814) revealed that hydrophobic and aromatic ring features were important for both subtypes, whereas hydrogen bond (HB) acceptor and donor were crucial for β- and α-subtypes, respectively. Interactions observed between ligand and catalytic residues at the active site in docking study substantiated the developed model which may be successfully used in high throughput screening (HTS) to obtain promising lead molecules for selective estrogen therapy.

Avaliação imunoistoquímica dos receptores de estrogênio e progesterona no câncer de mama, pré e pós-quimioterapia neoadjuvante / Immunohistochemical evaluation of estrogen and progesterone receptors of pre and post-neoadjuvant chemotherapy for breast cancer

OBJETIVO: Avaliar a imunoexpressão dos receptores de estrogênio e progesterona em biópsias e peças cirúrgicas de pacientes com câncer de mama pré e pós-quimioterapia neoadjuvante e correlacionar suas alterações com o padrão de resposta à quimioterapia e diagnóstico de menopausa. MÉTODOS: Selecionaram-se 47 pacientes com diagnóstico histopatológico de carcinoma primário de mama localmente avançado. Para cada paciente existiam dois blocos: o espécime da biópsia e o da ressecção cirúrgica. A partir destes blocos foi avaliada a expressão dos receptores hormonais por imunoistoquímica com a técnica da streptoavidina-biotina-imunoperoxidase e anticorpos primários anti-RE e anti-RP. A análise estatística utilizou o teste paramétrico t de Student e o não-paramétrico exato de Fisher, com nível de significância de 5%. RESULTADOS: Das 47 pacientes, 30 apresentavam imunoexpressão positiva dos receptores hormonais. Observou-se redução significativa tanto nos níveis de receptor de estrogênio e progesterona quanto em sua imunoexpressão. Em 53,3% observaram-se mudanças nos níveis expressos de receptor de estrogênio, 56,6% em receptor de progesterona, 26,6% na imunoexpressão do receptor de estrogênio e 33,3% na imunoexpressão do receptor de progesterona. Não foi encontrada significância estatística ao correlacionar-se a influência da resposta à quimioterapia e do diagnóstico de menopausa nas pacientes com a variação na expressão dos receptores hormonais. CONCLUSÃO: A quimioterapia neoadjuvante alterou significativamente a imunoexpressão dos receptores hormonais nas pacientes da amostra, reduzindo sua positividade nas células tumorais.

OBJECTIVE: To evaluate the immunoexpression of estrogen and progesterone receptors in biopsies and surgical specimens of patients with breast cancer before and after neoadjuvant chemotherapy and to correlate their changes with the pattern of response to chemotherapy and diagnosis of menopause. METHODS: We selected 47 patients with histological diagnosis of locally advanced primary breast carcinoma. For each patient there were two blocks: the biopsy specimen and surgical resection one. From these blocks hormone receptor expression was assessed by immunohistochemistry using the technique of streptoavidin-biotin-immunoperoxidase and anti-ER and anti-PR primary antibodies. The statistical analysis used the Student's t test and the nonparametric Fisher's exact test, with significance level of 5%. RESULTS: Of the 47 patients, 30 showed positive immunostaining for hormone receptors. There was significant reduction in the levels of both estrogen and progesterone receptors and in their immunoreactivity. In 53.3% we observed changes in levels of estrogen receptor expression, 56.6% in the progesterone receptor, 26.6% in the immunoexpression of estrogen receptor immunoreactivity and 33.3% in the immunoreactivity of the progesterone receptor. There was no statistical correlation between the influence of the response to chemotherapy and the diagnosis of menopause in women with variation in the expression of hormone receptors. CONCLUSION: Neoadjuvant chemotherapy has significantly altered hormone receptor immunoreactivity in patients in the sample, reducing its positivity in tumor cells.

Molecular phenotypes of ductal carcinoma-in-situ and invasive ductal carcinoma: A comparative study.

Aims and Objectives: This study was aimed at analyzing the prevalence of molecular phenotypes in invasive ductal carcinoma (IDC) and coexisting ductal carcinoma-in-situ (DCIS) and to correlate with clinicopathological features. Materials and Methods: In this study, 75 cases of IDC with coexisting DCIS were included. Molecular phenotype was determined using expression of estrogen receptor, progesterone receptor, HER2/neu, and cytokeratin 5/6. Statistical analysis was performed for correlation between molecular phenotypes and clinicopathologic parameters. Results: Of the 75 cases, the invasive component in all cases was IDC-not otherwise specified. About one-third of our patients were post-menopausal. The most common molecular phenotype was luminal A (45.3%) followed by HER2-expressing type (24%). In all cases, the molecular phenotype was identical in DCIS and the invasive component. HER2-expressing tumors were found to be larger in size with frequent nodal involvement. On statistical analysis, tumor size and grade were found to correlate with the molecular phenotype. Conclusion: In conclusion, the molecular phenotype in DCIS correlates well with that of coexisting IDC, suggesting that DCIS is a precursor lesion in these tumors. This correlation of molecular phenotype can be utilized in prediction of phenotype of the invasive component in a case with in-situ carcinoma.

Sodium iodide symporter, estrogen receptor, and progesterone receptor expression in carcinoma breast - An immunohistochemical analysis.

Background: Sodium iodide symporter (NIS), a transporter of iodine is essential for thyroid hormone biosynthesis. It also plays a role in the radioiodine treatment of thyroid cancers. NIS mediated radioiodine transport to breast cancers is under active investigation due to its potential therapeutic utility. Cellular localization and quantification using immunohistochemistry may provide clues for its utility in management of carcinoma breast. Materials and Methods: Human NIS (hNIS) expression was therefore assessed by utilizing a rabbit polyclonal antibody raised against a cloned hNIS in different grades of infiltrating duct carcinoma of breast and its metastatic deposits namely in lymph nodes, bone marrow, and endometrium. Further, hNIS expression was compared with prognostic markers namely estrogen receptor (ER) and progesterone receptor (PR). Results: hNIS was positive in 90.6% cases (29/32) and Scarff-Bloom-Richardson grading was done in 25 cases and 23 cases were NIS positive. Among nongraded cases, 2/2 cases of carcinoma in-situ were positive and 4/5 were positive in cases having post therapy residual tumor status. The strong positivity for hNIS was seen irrespective of ER or PR status and of grade of breast carcinoma and correlated well with western blot analysis. In all the three metastatic sites, NIS was positive in the tumor. Conclusion: These findings indicate the utility of immnohistochemistry for NIS as a new potential prognostic marker and may provide guidance for possible radio iodine therapy in breast cancer patients.

Core biopsies of the breast: Diagnostic pitfalls.

The incidence of breast cancer is increasing worldwide. In this review article, the authors compare and contrast the incidence of breast cancer, and the inherent differences in the United States (US) and India in screening techniques used for diagnosing breast cancer. In spite of these differences, core biopsies of the breast are common for diagnosis of breast cancer in both countries. The authors describe "Best Practices" in the reporting and processing of core biopsies and in the analysis of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor Receptor 2 (Her2/neu). The pitfalls in the diagnosis of fibroepithelial lesions of the breast on core biopsy are discussed, as also the significance of pseudoangiomatous stromal hyperplasia of the breast (PASH) is discussed in core biopsy. In this review, the management and diagnosis of flat epithelial atypia and radiation atypia are elaborated and the use of immunohistochemistry (IHC) in papillary lesions, phyllodes tumor, and complex sclerosing lesions (radial scars) is illustrated. Rarer lesions such as mucinous and histiocytoid carcinoma are also discussed.

Avaliação do impacto do status dos receptores hormonais e da proteína Her-2 no prognóstico do câncer de mama / Impact assessing of immunoshistochemical hormone receptor status and Her-2 in breast cancer prognosis

O câncer de mama é o principal tipo de câncer que atinge as mulheres. São mais de um milhão acometidas, com estimativa de 410 mil mortes por coma da doença em um período de um ano. O objetivo do preseme escudo é estabelecer, por meio da revisão da literatura, o papel da imunoexpressão dos receptores hormonais e da proteína do Her-2 no prognóstico e na resposta terapêutica do câncer de mama. Foi realizada uma revisão sistemática, com busca de artigos nas bases Pubmed National Library of Medicine, Scientific Eletronic Library Online (Scielo), Science Based Medicine e Medline Health Information from National Library of Medicine. Foram excluídos os artigos de revisão e estudos experimemais com animais. Encomraram-se 1.300 artigos no Pubmed, 711 no Medline, 415 no Science Medic e 139 no Scielo, totalizando 2.255 documemos. Destes, se!ecionaram-se 18 trabalhos para a revisão. Conclui-se que o estudo imunohistoquímico tem grande importância na avaliação prognóstica e preditiva do câncer de mama, porém os estudos ainda são muito controversos. Existe necessidade de acompanhamemo maior das pacientes e de correlacionar esses dados com fatores clínico-patoIógicos.

Breast cancer is a major cause of cancer related death in women, with more than one million new cases and as often as 410 thousands deaths in one year. The object of this study is confirm if there is a correlation of immune-histochemistry (hormonal receptors and Her-2) and prognostic of breast cancer. We carried out a systematic review on Pubmed, Scielo, Science Medic and Medline and excluded the review with animals or research that didn't evaluate the effects of immune-histochemistry in prognostic breast cancer. We discovered 1.300 systematic reviews in Pubmed, 711 in Medline, 415 Science Medic and 139 Scielo with 2.255 articles. Among 2.255, we selected 18. We may conclude there is a great importance in a correlation of the immunohistochemistry and the prognostic breast cancer, but the articles are very controversial. We need to have afollow-up with these patients for a long time and better evaluation with clinic-pathologic factors.

Cutaneous ciliated cyst in the subcutaneous area.

A 25-year-old woman was seen for a painless subcutaneous mass of 2 years duration. On excisional biopsy, a collapsed cystic structure lined by stratified, ciliated, columnar epithelium was noted. These linning cells did not produce mucin. Immunohistochemical staining for progesterone receptor, estrogen receptor and epithelial membrane antigen was positive, whereas it was negative for carcinoembryonic antigen. Findings were consistent with cutaneous ciliated cyst (CCC). CCCs are rare, predominantly occurring on the lower extremities of young women. Most of them have been regarded as Mullerian remnants. A case of a CCC in the subcutaneous area is reported.