Identification of a subtype of poorly differentiated invasive ductal carcinoma of the breast based on vimentin and e-cadherin expression / Identificação de um subtipo pouco diferenciado de carcinoma ductal invasivo de mama, baseado na expressão da vimentina e E-caderina

Abstract Objective The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs). Methods We have constructed a tissuemicroarray (TMA) from87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B (n = 39), HER2 enriched (n = 25), and triple-negative (TNBC) (n = 23), based on the IHC expression. Results We have observed that luminal A and B tumors lack the VIM+/CDH1-/low phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors (p = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM+/CDH1-/low phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) (p = 0.02). The median Ki67 index in the VIM+/CDH1-/low tumors was 13.6 (range: 17.8-45.4) compared with 9.8 (range: 4.1-38.1) in other tumors (p = 0.0007). The presence of lymph nodemetastasis was less frequent in patients with VIM+/CDH1-/low tumors (23% versus 61%; X2 test; p = 0.01). Conclusion Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index.

Resumo Objetivo O uso de marcadores moleculares pode identificar subtipos tumorais com diferentes taxas de recidiva. O objetivo do presente estudo é caracterizar a expressão imunohistoquímica da vimentina (VIM), da E-caderina (CDH1) e de CK5 em pacientes com carcinoma ductal invasivo (CDI) da mama. Métodos Utilizamos uma matriz de amostras teciduais (TMA, na sigla em inglês) de 87 pacientes com CDI da mama. Para avaliar a expressão dos receptores de estrogênio (RE) e receptores de progesterona (RP), HER2, VIM, CDH1, CK5 e Ki67, utilizamos imunohistoquímica. Os tumores foram classificados como luminal A e B (n = 39), HER2+ (n = 25) e triplo negativo (TNBC) (n = 23). Resultados Foi observado que tumores luminais A e B não expressaram o fenótipo VIM+/CDH1-/low. Este fenótipo foi observado em 16,5% dos tumores HER2+ e em 60% dos tumores TNBC (p = 0,0001). Dos 20 tumores TNBC, a CK5 (marcador de tumor basalóide) foi super expressa em 11 amostras. O fenótipo VIM+/CDH1-/low foi observado em 5 tumores CK5+ TNBC (45%) e em 7 dos 9 tumores CK5- TNBC (78%) (p = 0,02). A expressão média de Ki67 nos tumores VIM+/CDH1-/low foi 13.6 (amplitude de 17,8 a 45,4) comparado com 9,8 (amplitude de 4,1 a 38,1) nos outros tumores (p = 0,0007). A presença demetástase linfonodal foimenor em tumores com fenótipo VIM+/CDH1-/low (23% contra 61%; teste X2; p = 0,01). Conclusão Nossos achados sugerem que a expressão de VIM e CDH1 pode identificar um subtipo de CDI da mama com fenótipo mesenquimal associado a pior prognóstico, lesões de alto grau e alto índice mitótico.

Evaluation of survivin immunoexpression in the differentiation of high- and low-grade breast ductal carcinoma in situ / Expressão da proteína survivina em carcinoma ductal in situ de mama de alto e de baixo grau

ABSTRACT Objective To evaluate the expression of survivin protein in low- and high-grade ductal carcinoma in situ. Methods Breast tissue fragments obtained by incisional biopsy and surgical procedures of 37 women with ductal carcinoma in situ of the breast were subdivided into two groups: Group A, composed of women with low-grade ductal carcinoma in situ, and Group B, women with high-grade ductal carcinoma in situ. Survivin protein expression test was performed by immunohistochemistry, using a monoclonal antibody clone I2C4. The criterion to evaluate survivin immunoexpression was based on the percentage of neoplastic cells that presented brown-gold staining. This criterion was positive when the percentage of stained cells was ≥10%. Results The survivin protein was expressed in 22 out of 24 cases of high-grade ductal carcinoma in situ (78%), whereas, in Group A, of low-grade ductal carcinoma in situ (n=13), it was positive in only 6 cases (21.40%; p=0.004). Conclusion The frequency of expression of survivin was significantly higher in the group of patients with high-grade ductal carcinoma in situ compared to those in the low-grade ductal carcinoma in situ group.

RESUMO Objetivo Avaliar a imunoexpressão da proteína survivina nos carcinomas ductais in situ de mama de baixo e de alto graus. Métodos Fragmentos de tecido mamários obtidos por biópsia incisional e procedimentos cirúrgicos de 37 mulheres acometidas por carcinoma ductal in situ de mama foram subdivididos em dois grupos: Grupo A, formado por mulheres com carcinoma ductal in situ de baixo grau; e Grupo B, por mulheres com carcinoma ductal in situ de alto grau. A pesquisa de expressão da proteína survivina foi realizada pela técnica de imuno-histoquímica, utilizando-se anticorpo monoclonal clone I2C4. O critério de avaliação da imunoexpressão da survivina baseou-se na percentagem de células neoplásicas que apresentava coloração castanho-dourada. Considerouse tal critério positivo quando a percentagem de células apresentasse marcação ≥10%. Resultados A proteína survivina apresentou-se expressa em 22 dos 24 casos de carcinoma ductal in situ de alto grau (78%), enquanto no Grupo A, de carcinoma ductal in situ de baixo grau (n=13), apresentou-se positiva em apenas 6 casos (21,40%; p=0,004). Conclusão O índice de frequência de expressão da survivina foi significativamente mais elevado no grupo de pacientes com carcinoma ductal in situ de alto grau, quando comparado às do grupo com carcinoma ductal in situ de baixo grau.

Expression of Sarcosine Metabolism-Related Proteins in Invasive Lobular Carcinoma: Comparison to Invasive Ductal Carcinoma

PURPOSE: The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results. MATERIALS AND METHODS: Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)]. RESULTS: The sarcosine metabolic phenotype differed between ILC and IDC (plow sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC. CONCLUSION: Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.

Expression of vimentin in breast carcinoma, its correlation with Ki67 and other histopathological parameters.

CONTEXT: Vimentin is a mesenchymal marker, known to express in some epithelial carcinomas. AIMS: 1. To find out the expression of vimentin in infiltrating ductal carcinoma of breast (not otherwise specified), 2. To find out the correlation between expression of vimentin and prognostic markers such as tumor size, tumor grade, lymph node status, proliferation index (measured by Ki 67), and Nottingham prognostic index (NPI). MATERIALS AND METHODS: Study was done at Department of Pathology; 50 cases of infiltrating ductal carcinoma (NOS) were studied for tumor grade; immunohistochemistry was done using antibodies against vimentin and Ki 67. Percentages of positive cells were documented. An immunoscore was also calculated for vimentin. Vimentin expression was correlated with tumor size, lymph node status, Nottingham prognostic index, and Ki 67. Statistical analysis used: statistical correlation was done using Pearson’s chi-square test. A P value less than 0.01 was considered significant. RESULTS: Vimentin expression was seen in 18% of cases. Its expression correlated with high tumor grade and high growth fraction (P value < 0.01). It did not correlate with lymph node status, tumor size, and NPI. CONCLUSIONS: Increased vimentin expression is associated with bad prognostic factors. Immunohistochemistry with vimentin may be helpful in knowing the prognosis in cases of infiltrating ductal carcinoma of breast (NOS).

Immunohistochemical profile of high-grade ductal carcinoma in situ of the breast

OBJECTIVE: To determine the frequency of the immunohistochemical profiles of a series of high-grade ductal carcinoma in situ of the breast. METHODS: One hundred and twenty-one cases of high-grade ductal carcinoma in situ, pure or associated with invasive mammary carcinoma, were identified from 2003 to 2008 and examined with immunohistochemistry for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5, and epidermal growth factor receptor. The tumors were placed into five subgroups: luminal A, luminal B, HER2, basal-like, and “not classified”. RESULTS: The frequencies of the immunophenotypes of pure ductal carcinoma in situ were the following: luminal A (24/42 cases; 57.1%), luminal B (05/42 cases; 11.9%), HER2 (07/42 cases; 16.7%), basal-like phenotype (00/42 cases; 0%), and “not classified” (06/42 cases; 14.3%). The immunophenotypes of ductal carcinoma in situ associated with invasive carcinoma were the following: luminal A (46/79 cases; 58.2%), luminal B (10/79 cases; 12.7%), HER2 (06/79 cases; 7.6%), basal-like (06/79 cases; 7.6%), and “not classified” (11/79 cases; 13.9%). There was no significant difference in the immunophenotype frequencies between pure ductal carcinoma in situ and ductal carcinoma in situ associated with invasive carcinoma (p>0.05). High agreement was observed in immunophenotypes between both components (kappa=0.867). CONCLUSION: The most common immunophenotype of pure ductal carcinoma in situ was luminal A, followed by HER2. The basal-like phenotype was observed only in ductal carcinoma in situ associated with invasive carcinoma, which had a similar phenotype. .

Expression of JMJD2A in infiltrating duct carcinoma was markedly higher than fibroadenoma, and associated with expression of ARHI, p53 and ER in infiltrating duct carcinoma.

Jumonji Domain Containing 2A (JMJD2A) may be a cancer-associated gene involved in human breast cancer. With a view to investigating expression of JMJD2A in human breast cancer and benign lesion tissues as well as relationship between JMJD2A and tumor related proteins, histological and immunohistochemical analysis, Western blot and quantitative real-time PCR in infiltrating duct carcinoma and fibroadenoma for JMJD2A and immunohistochemical analysis and quantitative real-time PCR in infiltrating duct carcinoma for tumor related proteins (ARHI, p53, ER, PR and CerbB-2) were performed. Histological examination validated the clinical diagnosis. The JMJD2A positive rate of infiltrating duct carcinoma was significantly higher than fibroadenoma by immunohistochemical analysis. The mean optical density of JMJD2A in infiltrating duct carcinoma was higher than fibroadenoma by western blot. JMJD2A mRNA level in infiltrating duct carcinoma was higher than fibroadenoma by quantitative real-time PCR. Spearman correlation analysis revealed that the expression of JMJD2A was associated with ARHI, p53 and ER from immunohistochemical results respectively. Pearson correlation analysis revealed that the expression of JMJD2A was associated with ARHI, p53 and ER from quantitative real-time PCR results respectively. Expression of JMJD2A in infiltrating duct carcinoma was higher, and associated with ARHI, p53 and ER. The results may take JMJD2A as a potential diagnostic and therapeutic target in human breast cancer.

ROS1 Expression in Invasive Ductal Carcinoma of the Breast Related to Proliferation Activity

PURPOSE: ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR). RESULTS: ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant. CONCLUSION: Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells.

The prevalence and significance of oestrogen receptor (ER) positivity in breast cancer at the University Hospital of the West Indies, Jamaica / Prevalencia y significación de la positividad del receptor de estrógeno (RE) en el cáncer de mama en el Hospital Universitario de West Indies, Jamaica

OBJECTIVE: To identify the prevalence of oestrogen receptor (ER) positivity, and determine the relationship of ER status with patient and tumour characteristics, in patients with breast cancer. SUBJECTS AND METHODS: A retrospective review was conducted regarding the prevalence and clinical significance of ER in patients with breast cancer at the University Hospital of the West Indies (UHWI). Oestrogen receptor status results of 243 patients treated at UHWI were collected for the period January 1, 2002 to December 31, 2009. One hundred and ninety-nine were available for review. RESULTS: Oestrogen receptor status was positive in 125 (63%) and negative in 74 (37%) patients. Mean age at diagnosis was 52.6 ± 13.0 years for the ER positive group and 58.5 ± 14.23 years for the ER negative group. Postmenopausal women accounted for 55.2% and 64.9% of the ER positive and negative groups, respectively. Mean BMI was 28.0 kg/m² and 29.6 kg/m² for the ER positive and negative groups, respectively. Menarche occurred mainly between ages 12 and 13 years for both groups. Mean age at 1st parity was 23.4 years for the ER positive and 21.4 years for the ER negative group with median parity of two for both groups. The most prevalent risk factors were oral contraceptive pill (OCP) use (24.3% for the ER positive group, 17.1% for the ER negative group), family history of breast cancer (12.0%; 13.4%) and previous smoking (8.4%; 6.9%). Tumour node metastasis (TNM) stage was Stage II in most cases (46%; 49%). Infiltrating ductal histology was most common (81.5%; 87.7%). Her 2/ neu status was negative for most patients (91.3%; 91.5%). Most patients were disease free (77.6%; 70.0%) after an average follow-up period of 3.5 years. More persons in the ER negative group had locoregional recurrence (8%) and metastases (22%). CONCLUSIONS: Oestrogen receptor positive cohort was more prevalent. The ER negative group was older (p = 0.003).

OBJETIVO: Identificar la prevalencia del receptor de la positividad de receptor de estrógeno (RE), y determinar la relación del estatus de RE con el paciente y las características del tumor, en las pacientes con cáncer de mama. SUJETOS Y MÉTODOS: Se realizó un estudio retrospectivo con respecto a la prevalencia e importancia clínica del RE en los pacientes con cáncer de mama en el Hospital Universitario de West Indies (UHWI). Se recogieron los resultados del estatus del receptor de estrógeno de 243 pacientes tratados en UHWI en el periodo del 1 de enero de 2002 al 31 de diciembre de 2009. Ciento noventa y nueve estuvieron disponibles para examen. RESULTADOS: El estatus del receptor de estrógeno fue positivo en 125 (63%) y negativo en 74 (37%) pacientes. La edad promedio al momento del diagnóstico fue 52.6 ± 13.0 años para el grupo de RE positivo y 58.5 ± 14.23 años para el RE grupo negativo. Las mujeres menopáusicas representaron el 55.2% y el 64.9% del RE de los grupos positivos y negativos respectivamente. El índice de masa corporal (IMC) promedio fue 28.0 kg/m2 y 29.6 kg/m2 para el RE de los grupos positivos y negativos respectivamente. La menarquia ocurrió principalmente entre las edades de 12 y 13 años para ambos grupos. La edad promedio en la primera paridad fue 23.4 años para el grupo de RE positivo y 21.4 años para el de RE negativo, siendo la paridad mediana igual a dos para ambos grupos. Los factores de riesgo de mayor preponderancia fueron el uso de anticonceptivos orales (ACO) (24. 3% para el grupo de RE positivo, 17.1% para el grupo RE negativo); historia familiar de cáncer de mama (12.0%; 13.4%); y hábito de fumar con anterioridad (8.4%; 6.9%). De acuerdo con la estadificación tumor-nódulo-metástasis (TNM), se trataba de la Etapa II en la mayor parte de los casos (46%; 49%). La histología ductal infiltrante fue la más común (81.5%; 87.7%). El estatus Her2/neu fue negativo para la mayoría de las pacientes (91.3%; 91.5%). La mayoría de las pacientes se hallaban libres de enfermedad (77.6%; 70.0%) después de un periodo promedio de seguimiento de 3.5 años. En el grupo de RE negativo había más personas con recurrencia locoregional (8%) y metástasis (22%). CONCLUSIONES: La cohorte positiva del receptor de estrógeno positiva fue más prevaleciente. El grupo negativo de RE fue de mayor edad (p = 0.003).

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.

Inmunodetección de FHIT y E-cadherina en fibroadenomas y cáncer ductal y lobulillar de mama / Inmunodetection of FHIT and E-cadherin in fibroadenomas and ductal and lobular human breast cancer

En Chile, el cáncer es la segunda causa de muerte después de las enfermedades cardiovasculares. Los principales cánceres asociados a muerte en mujeres fueron mama, estómago, vesícula biliar, broncopulmonar y cérvico uterino. Alteraciones de las E-cadherinas han sido relacionadas con varios tipos de cáncer, ya que uno de los principales eventos involucrados con su disfunción es el gatillar la invasión y metástasis del tumor. La inactivación del gen CDH1 ha sido demostrada en el cáncer gástrico difuso y el cáncer de mama lobulillar. Asimismo, la inactivación del gen FHIT parece estar asociado con la progresión a neoplasias más agresivas. Se realizaron determinaciones inmunohistoquímicas (IHQ) en fibroadenomas mamarios y cánceres previamente diagnosticados por RE, RPg y Her2, mostrando positividad en todos los casos. La detección (IHQ) de la expresión de FHIT y E-cadherina en tejidos con patologías benignas y malignizados, puede aportar una importante información diagnóstica y pronóstica en el cáncer de mama.

In Chile, cancer is the second leading cause of death after cardiovascular diseases. The major death-related cancers in women were breast, stomach, gallbladder, lung and cervical cancer. Alterations of E-cadherin have been linked to various cancers, as one of the main events involved in its dysfunction is the trigger of tumor invasion and metastasis. CDH1 gene inactivation has been demonstrated in diffuse gastric cancer and lobular breast cancer. Furthermore, inactivation of the FHIT gene to be associated with progression to more aggressive tumors. Immunohistochemistry (IHC) determinations were performed in fibroadenomas and breast cancers previously diagnosed by ER, PgR and Her2, showing positivity in all cases. Immunohistochemical detection of FHIT and E-cadherin expression in tissues with benign disease and malignant, may provide an important diagnostic and prognostic information in breast cancer.

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.

Oxidative stress parameters in women with breast cancer undergoing neoadjuvant chemotherapy and treated with nutraceutical doses of oral glutamine / Parâmetros de estresse oxidativo em mulheres com câncer de mama submetidas à quimioterapia neoadjuvante e tratadas com doses nutracêuticas da glutamina oral

PURPOSE: To evaluate the effects of oral administration of GLN on the oxidative stress in women with breast cancer undergoing neoadjuvant FAC chemotherapy (5 fluouracil 500 mg/m²+Doxorubicin 50 mg/m²+Cyclophosphamide 500 mg/m² body surface area). METHODS: Twenty women (mean age: 51.7 years) with breast ductal carcinomas classified as T3 or T4 were included in the study, regardless of pre or post menopause status. Sachets containing glutamine 15g ("A") or milk protein 15g ("B") were prepared by a registered pharmacist. Allocation of patients was made by software program. Patients who received sachets labeled "A" were included in G1 group. The remaining patients, treated with the preparation labeled "B", were included in group G2. Sachets contents were blended in 150 ml of drinking water, and were given daily to each patient during the entire course of neoadjuvant chemotherapy. Peripheral blood samples were collected in the first day of each of the three cycles of chemotherapy before drug infusion. Tumor and normal breast samples were collected at the end of Patey´s surgical procedure. Samples were analysed for GSH and TBARS contents. RESULTS: TBARS and GSH values were not different in breast healthy and tumor tissues nor blood when comparing control (G-2) and glutamine-treated (G-1) patients. Also, no significant differences were found in TBARS and GSH levels comparing different timepoints within the same group. CONCLUSION: Oral GLN (15g/kg/day) offers no protection against systemic or local oxidative stress in women with breast Ca undergoing neoadjuvant chemotherapy (FAC).

OBJETIVO: Avaliar os efeitos da administração oral de GLN sobre o estresse oxidativo em mulheres com câncer mamário submetidas à quimioterapia neoadjuvante com esquema FAC (5 fluouracil 500 mg/m2+doxorrubicina 50 mg/m2+ciclofosfamida 500 mg/m2 de superfície corporal). MÉTODOS: Vinte mulheres (idade média: 51,7 anos) com carcinoma ductal de mama, classificado como T3 ou T4 foram incluídas no estudo, independente do seu estado menstrual. Embalagens contendo 15g de glutamina ou proteína do leite foram preparadas por farmacêutico. Alocação dos pacientes foi feita na seqüência gerada por "software". Pacientes que receberam embalagens tipo "A" foram incluídas no grupo G1. Pacientes tratadas com a preparação denominada "B", foram incluídas no grupo G2. O material foi misturado com uso de liquidificador em 150 ml de água potável, e administrado diariamente aos pacientes durante todo o curso da quimioterapia neoadjuvante (esquema FAC). Amostras de sangue periférico foram coletadas no inicio dos três ciclos de quimioterapia, antes da infusão de drogas. Amostras de tumor e tecido mamário normal foram colhidas no final do procedimento cirúrgico (cirurgia de Patey). As amostras foram analisadas para determinação das concentrações de GSH e TBARS. RESULTADOS: Concentrações de TBARS/ GSH não foram diferentes no tumor. tecido mamário ou sangue, comparando os grupos G-2 vs.G-1. Além disso, não foram encontradas diferenças significativas nos níveis de TBARS e GSH comparando momentos diferentes dentro do mesmo grupo. CONCLUSÃO: GLN (15g/kg/dia) administrada por via oral não oferece proteção contra o estresse oxidativo sistêmico ou local em mulheres com câncer de mama, submetidas à quimioterapia neoadjuvante (FAC).

Expression of e-cadherin, n-cadherin and snail and their correlation with clinicopathological variants: an immunohistochemical study of 132 invasive ductal breast carcinomas in Egypt

OBJECTIVE: To evaluate the expression of the cell adhesion molecules E-cadherin and N-cadherin and the transcription factor Snail in invasive ductal breast carcinomas and to determine their relationships with clinicopathological features. METHODS: Immunohistochemistry was used to examine E-cadherin, N-cadherin, and Snail protein expression in 132 invasive breast carcinomas. RESULTS: The expression of E-cadherin was decreased (negative or weak) in 37.1 percent of invasive carcinomas, while N-cadherin and Snail overexpression were detected in 51.9 percent and 40.9 percent of carcinomas, respectively. Low E-cadherin expression was significantly correlated with poorly differentiated carcinoma (53.1 percent), positive node status (80.9 percent), poor Nottingham Prognostic Index (64.7 percent), and the presence of estrogen and progesterone receptors. Overexpression of N-cadherin and Snail were also significantly correlated with poorly differentiated carcinoma, positive node status, and poor Nottingham Prognostic Index but were correlated with the absence of hormone receptors. Loss of E-cadherin immunoexpression was strongly associated with the presence of membranous N-cadherin (87.8 percent) and nuclear Snail (69.4 percent). CONCLUSION: Loss of E-cadherin and overexpression of N-cadherin and Snail in breast carcinomas may play a central role in the development of invasive ductal breast carcinoma. These biomarkers may provide a valuable reference for the study of invasive ductal carcinoma progression and to characterize the biological behavior of the tumor. In the future, increased N-cadherin and decreased E-cadherin expression may be used as indicators of the progression and prognosis of invasive ductal carcinoma.

Análise da expressão de carboidratos no estroma do carcinoma ductal invasivo da mama e sua correlação com dados clínicos e histopatológicos / Carbohydrates expression analysis in stroma of breast invasive ductal carcinoma and its correlation with clinical and histopathological datas

Objetivos: Analisar o perfil de carboidratos no estroma do carcinoma ductal invasivo, usando histoquímica com lectinas, e correlacionar os achados com dados clínicos e histopatológicos. Métodos: Estudo retrospectivo baseado na análise dos casos de 30 pacientes diagnosticados com carcinoma ductal invasivo durante o período de Maio a Outubro de 2008, As mostras tumorais foram submetidas a histoquímica com lectinas, na qual foram utilizadas as lectinas conjugadas à peroxidase: PNA-Per, 25 mg/mL, UEA-I-Per, 40 mg/mL e Con A-Per, 40 mg/mL específicas para D-galactose, L-fucose e glicose/manose, respectivamente. Posteriormente, os achados histoquímicos foram relacionados com os dados clínicos e histopatológicos (idade, invasão linfonodal, status para p53, tamanho tumoral e variante histológica) das pacientes. Resultados: Na histoquímica com lectinas, a Con A reconheceu a matriz extracelular em 53,33% dos casos, enquanto a PNA e a UEA-I reconheceram 30 e 40%. Já o endotélio de vasos sanguíneos foi mais reconhecido pela UEA-I (40% dos casos) que a Con A (10% dos casos). Biópsias de pacientes cuja matriz extracelular foi reconhecida pela Con A foram positivas também para p53 (p = 0,029), e todos os casos positivos para p53 (p = 0,041) tiveram os respectivos endotélios vasculares reconhecidos por essa lectina. O reconhecimento do estroma pela UEA-I em relação à variante histológica pouco diferenciada mostrou-se significativo (p = 0,034) em relação às demais variáveis analisadas. Conclusões: Os resultados indicaram o potencial das lectinas como sondas eficientes e os glicoconjugados de estroma como biomarcadores ou fonte de informações da biologia tumoral do carcinoma ductal invasivo.

Objectives: To analyze the carbohydrates profile in the stroma of invasive ductal carcinoma, using lectin histochemistry, and correlate the findings with clinical and histopathological data. Methods: Retrospective study based on analysis of 30 cases from patients previously diagnosed with invasive ductal carcinoma during the period from May to October 2008. Tumour samples were subjected to the lectin histochemistry technique, in which the peroxidase-conjugated lectins were used: PNA-Per, 25 mg/mL, UEA-I-Per, 40 mg/mL e Con A-Per, 40 mg/mL specifics for D-galactose, L-fucose and glucose/mannose respectively. Subsequently the histochemical findings were correlated with clinical and histopathological data (age, lymph node invasion, status to p53, tumor size and histological variant) of the patients. Results: In lectin histochemistry, the Con A stained the extracellular matriz of 53.33% of cases, while the PNA and UEA-I recognized 30 and 40% of the ECM, respectively. The blood vessels endothelium was most recognized by the lectin UEA-I (40%) than Con A (10%). Biopsies from patients with ECM stained by Con A were also positive for p53 (p = 0.029), and all positive cases to p53 (p = 0.041) had the respective endothelium recognized by the same lectin. The ECM staining by the UEA-I in relation to poorly differentiated histological variant showed a significant difference (p = 0.034) between the variants analyzed. Conclusions: The results indicated the potential of lectins as efficient probres and stromal glycoconjugates as biomarker or source of information in the diagnosis of invasive ductal carcinoma.

The interaction between aromatase, metalloproteinase 2,9 and cd44 in breast cancer / A interação entre aromatase, metalloproteinase 2, 9 e cd44 no câncer de mama

OBJECTIVE: This study intends to verify the expression levels and correlation of aromatase, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9) and CD44 in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) when both are found in the same breast. METHODS: One hundred and ten cases were evaluated by tissue microarray (TMA) and immunohistochemically screened with anti-aromatase polyclonal antibodies, anti-MMP-2 monoclonal antibodies, anti-MMP-9 policlonal antibodies and anti-CD44 monoclonal antibodies. RESULTS: Aromatase was expressed in IDC and DCIS in 63 (57.3 percent) and 60 (67 percent) of the cases respectively; MMP-2 was similarly expressed in IDC and DCIS in 15 (13.60 percent) cases; MMP-9 was positively expressed in IDC and DCIS in 83 (75.50 percent) and 82 (74.50 percent) cases, respectively; CD44 was positively expressed in IDC and DCIS in 49 (44.50 percent) and 48 (42.60 percent) of the cases, respectively; all of them were highly correlated (p<0,001). The correlation analysis found positive, statistically significant correlation, in IDC between aromatase and MMP-2 (p<0.001) and between aromatase and MMP-9 (p=0.034). Positive correlation between aromatase and MMP-2 (p<0.001) and between MMP-9 and CD44 (p=0.030) were found in DCIS. CONCLUSION: These results allow us to conclude that aromatase through local estrogen synthesis in breast tissue plays an important role in breast carcinogenesis, mainly influencing MMP-2 and MMP-9 which are important participants in tumor cell invasion and dependence of their connection to CD44 for action.

OBJETIVO: O objetivo desse estudo é verificar as expressões e correlações da aromatase, metalloproteinase 2 da matriz (MMP2), metalloproteinase 9 da matriz (MMP-9) e CD44 no carcinoma ductal in situ (CDIS) e carcinoma ductal infiltrativo (CDI) quando ambos estão presentes simultaneamente na mesma mama. MÉTODOS: Foram avaliados 110 casos pelo método de tissue microarray (TMA) e através da utilização de anticorpos policlonais antiaromatase, anticorpos monoclonais anti-MMP-2, anticorpos policlonais anti-MMP-9 e anticorpos monoclonais anti-CD44. RESULTADOS: A aromatase estava expressa de forma positiva no CDI e CDIS em 63 (57,3 por cento) e 60 (67 por cento) casos, respectivamente. A expressão de MMP-2 estava expressa de forma positiva em 15 (13,6 por cento) casos tanto no CDI, quanto no CDIS. A expressão da MMP-9 estava expressa de forma positiva em 83 (75,5 por cento) e 82 (74,5 por cento) casos de CDI e CDIS, respectivamente. A expressão de CD44 estava expressa de forma positiva em 49 (44,5 por cento) e 48 (42,6 por cento) casos de CDI e CDIS, respectivamente. Todos eles apresentando alta correlação (p<0,001). Na avaliação de correlação foi encontrada correlação positiva estatisticamente significante no CDI entre aromatase e MMP-2 (p<0,01) e entre aromatase e MMP-9 (p=0,034). Nos casos de CDIS houve correlação positiva estatisticamente significante entre aromatase e MMP-2 (p<0,001) e entre CD44 e MMP-9 (p=0,030). CONCLUSÃO: Após analisarmos os resultados de nosso estudo, podemos concluir que a aromatase, através da síntese de estrogênio local no tecido mamário, desempenha importante papel na carcinogênese mamária, principalmente influenciando a atuação da MMP-2 e da MMP-9, grandes responsáveis pela invasão celular tumoral que, por sua vez, provavelmente dependem de sua ligação a CD44 para poder desempenhar suas funções.

Expression of E-cadherin, Snail and Hakai in epithelial cells isolated from the primary tumor and from peritumoral tissue of invasive ductal breast carcinomas

Epithelial intercellular cohesion, mainly mediated by E-cadherin (CDH1) expression and function, may be deregulated during cancer cell invasion of adjacent tissues and lymphatic and vascular channels. CDH1 expression is down-modulated in invasive lobular breast carcinomas but its regulation in invasive ductal carcinomas (IDC) is less clear. CDH1 expression is repressed by transcription factors such as Snail (SNAI1) and its product is degraded after Hakai ubiquitination. We compared CDH1, SNAI1 and HAKAI mRNA expression in IDC and paired adjacent normal breast tissue and evaluated its relation with node metastasis and circulating tumor cells. Matched tumor/peritumoral and blood samples were collected from 30 patients with early IDC. Epithelial cells from each compartment (tumor/peritumoral) were recovered by an immunomagnetic method and gene expression was determined by real time RT-PCR. There were no differences in CDH1, SNAI1 and HAKAI mRNA expression between tumor and corresponding peritumoral samples and no differential tumoral gene expression according to nodal involvement. Another 30 patients with a long-term follow-up (at least 5 years) and a differential prognosis (good or poor, as defined by breast cancer death) had E-cadherin and Snail protein detected by immunohistochemistry in tumor samples. In this group, E-cadherin-positive expression, but not Snail, may be associated with a better prognosis. This is the first report simultaneously analyzing CDH1, SNAI1 and HAKAI mRNA expression in matched tumor and peritumoral samples from patients with IDC. However, no clear pattern of their expression could distinguish the invasive tumor compartment from its adjacent normal tissue.

Expressão citofotométrica quantitativa da CASPASE-3 e do CD-34 no carcinoma ductal infiltrante de mama / Cytophotometric expressions of CASPASE-3 and CD-34 in breast cancer

OBJETIVO: Descrever, correlacionar e comparar a expressão dos marcadores tumorais CD-34 (angiogênese) e caspase-3 (apoptose) em carcinoma ductal invasor de mama. MÉTODOS: Foram utilizados 22 casos de adenocarcinoma infiltrante de mama provenientes de blocos de parafina e, após preparo específico para imunoistoquímica, 15 apresentaram leitura satisfatória e foram avaliados pelo sistema de fotocitometria de imagem SAMBA 4000® e software IMMUNO®. Os parâmetros analisados foram o índice de marcagem e densidade óptica. RESULTADOS: Para o CD-34 não houve normalidade dos dados na análise do índice de marcagem, com obtenção de P=0,019, havendo normalidade para a análise da densidade óptica, com P=0,199. Para a caspase-3 houve normalidade de dados para o índice marcagem com P=0,306 e para a densidade óptica com P=0,114; não houve diferença estatística significativa entre eles em relação à média do índice de marcagem (P=0,872) e da densidade óptica (P=0,816), quando analisados os parâmetros que definem a expressão dos marcadores; existiu tendência à associação entre a densidade óptica e o índice de marcagem do marcador tumoral caspase-3, com P=0,025. Não foi observada tendência à associação quando comparados densidade óptica e índice de marcagem do marcador tumoral CD-34; índice de marcagem do marcador tumoral caspase-3 e índice de marcagem do marcador tumoral CD-34; e densidade óptica da caspase-3 com a do CD-34. CONCLUSÃO: Dos 22 casos incluídos foi possível verificar a expressão do marcador CD-34 em 18 lâminas e da caspase-3 em 22 lâminas; Para o CD-34 não houve normalidade dos dados na análise do índice de marcagem, havendo sim normalidade para a análise da densidade óptica. Para a caspase-3 houve normalidade de dados tanto para o índice de marcagem como para a densidade óptica. Existe tendência à associação entre a densidade óptica e o índice de marcagem da caspase-3. Não foi observada tendência quando comparados densidade óptica e índice...

OBJECTIVE: Describe, correlate and compare the expression of the tumor markers CD 34 (angiogenesis) and caspase-3 (apoptosis) in invasive breast adenocarcinoma, through image cytometry with the system SAMBA4000®. METHODS: Twenty-two cases of invasive breast adenocarcinoma from paraffin-embedded archival tissue, and after specific prepare, fifteen cases presented a satisfactory lecture with SAMBA4000® and could, finally, be evaluated by the software IMMUNO® (n = 15). The parameters analysed were the label index - in percentage, indicating the marked surface - and the optical density, in pixels - indicator of the marker intensity. The results were tabulated and expressed in averages, mediums, minimum and maximum values. The statistic analysis was realized by the Shapiro-Wilkins, Student test, Pearson's and Spearman's correlation, with statistic significance for values from p < 0,05. RESULTS: There was no data normality for the label index CD34 (p= 0,019), there was normality in the analysis of the optical density of both markers and label index of the marker Caspase-3. There was no difference relating to the average of the index marker and the optical density when they were compared. CONCLUSIONS: There was a tendency to correlate the label index and the optical density of the tumor marker caspase-3, the same did not occur with the tumor marker CD 34. Other analysis did not show any correlation between the two studied markers. Other studies involving theses two cell processes are needed to extend the knowledge of the cancer biomolecular mechanic and to permit new diagnostic and therapeutic strategies.

Expressão da proteína erbB-2 e dos receptores de hormônios na transição das regiões in situ para invasora de tumores da mama / ErbB-2 expression and hormone receptor status in areas of transition from in situ to invasive ductal breast carcinoma

OBJETIVOS: avaliar a expressão de erbB-2 e dos receptores hormonais para estrógeno e progesterona (RE/RP) nas regiões de transição entre as frações in situ e invasoras de neoplasias ductais da mama (CDIS e CDI, respectivamente). MÉTODOS: oitenta e cinco casos de neoplasias mamárias, contendo regiões contíguas de CDIS e CDI, foram selecionados. Espécimes histológicos das áreas de CDIS e de CDI foram obtidos através da técnica de tissue microarray (TMA). As expressões da erbB-2 e dos RE/RP foram avaliadas por meio de imunoistoquímica convencional. A comparação da expressão da erbB-2 e dos RE/RP nas frações in situ e invasoras da mama foi realizada com emprego do teste de McNemar. Os intervalos de confiança foram determinados em 5 por cento (p=0,05). Foram calculados coeficientes de correlação intraclasse (ICC) para avaliar a concordância na tabulação cruzada da expressão de erbB-2 e RE/RP nas frações de CDIS e CDI. RESULTADOS: a expressão da erbB-2 não diferiu entre as áreas de CDIS e CDI (p=0,38). Comparando caso a caso suas áreas de CDIS e CDI, houve boa concordância na expressão da erbB-2 (coeficiente de correlação intraclasse, ICC=0,64), dos RP (ICC = 0,71) e dos RE (ICC = 0,64). Considerando apenas tumores cujo componente in situ apresentasse áreas de necrose (comedo), o ICC para erbB-2 foi de 0,4, comparado a 0,6 no conjunto completo de casos. Os ICC não diferiram substancialmente daqueles obtidos com o conjunto completo de espécimes em relação aos RE/RP: para RE, ICC=0,7 (versus 0,7 no conjunto completo), e para RP, ICC=0,7 (versus 0,6 no conjunto completo). CONCLUSÕES: nossos achados sugerem que as expressões de erbB-2 e RE/RP não diferem nos componentes contíguos in situ e invasivo em tumores ductais da mama.

PURPOSE: to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively). METHODS: Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemar's test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5 percent (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas. RESULTS: the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample). CONCLUSIONS: our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumors.

Protein expression of c-erbB-2 and p53 in normal ducts, ductal carcinoma in situ and invasive carcinoma of the same breast / Expressão das proteínas c-erbB-2 e p53 nos ductos normais, carcinoma ductal in situ e carcinoma invasivo da mesma mama

CONTEXT AND OBJECTIVE: Breast cancer is thought to derive from progressively aberrant, non-invasive breast lesions, but it is not known exactly how invasive breast cancer develops from these lesions. The aim of this study was to verify the changes in c-erbB-2 and p53 protein expression between non-neoplastic ducts, ductal carcinoma in situ and invasive ductal carcinoma found in the same breast. DESIGN AND SETTING: This was a cross-sectional study at Centro de Atenção Integral à Saúde da Mulher, Campinas, Brazil. METHODS: Fifty-six women with invasive ductal carcinoma and ductal carcinoma in situ in the same breast were included. The expression of c-erbB-2 and p53 proteins was assessed in non-neoplastic and neoplastic cells using immunohistochemical techniques. RESULTS: The c-erbB-2 protein was absent in non-neoplastic ducts but was present in 46 percent and 36 percent of in situ and invasive carcinoma components, respectively. Only 2 percent of non-neoplastic ducts, and 18 percent and 16 percent of ductal carcinoma in situ and invasive carcinoma components, respectively, were positive for p53 protein. No significant difference in c-erbB-2 and p53 protein expression was observed between in situ and invasive components. The nuclear grade agreement between in situ and invasive carcinoma was very good. CONCLUSIONS: The invasiveness of ductal carcinoma in situ seems to be independent of the Her-2/neu and TP53 genes. The general features of an occurrence of breast carcinoma are formulated at the outset of carcinogenesis, and the Her-2/neu and TP53 genes are involved.

CONTEXTO E OBJETIVO: O câncer de mama se origina de lesões não-invasivas, tais como as hiperplasias atípicas e o carcinoma ductal in situ, porém não se sabe exatamente como o câncer se torna invasivo. O objetivo foi verificar alterações na expressão das proteínas c-erbB-2 e p53 entre ductos não-neoplásicos, carcinoma ductal in situ e carcinoma ductal invasivo presentes na mesma mama. TIPO DE ESTUDO E LOCAL: Estudo transversal, realizado no Centro de Atenção Integral à Saúde da Mulher, Campinas, São Paulo, Brasil. MÉTODOS: Cinqüenta e seis mulheres com o diagnóstico de carcinoma ductal invasivo e carcinoma ductal in situ na mesma mama foram selecionadas e incluídas neste estudo. A expressão das proteínas c-erbB-2 e p53 foi avaliada usando imunoistoquímica. RESULTADOS: A proteína c-erbB-2 estava ausente nos ductos não-neoplásicos, mas estava presente em 46 por cento e 36 por cento, respectivamente, dos componentes de carcinomas in situ e invasivos. Apenas 2 por cento dos ductos não-neoplásicos, 18 por cento e 16 por cento dos carcinomas in situ e carcinomas invasivos, respectivamente, foram positivos para a proteína p53. Não houve diferença significativa na expressão das proteínas c-erbB-2 e p53 entre os carcinomas ductal in situ e invasivo. A concordância do grau nuclear entre os carcinomas ductal in situ e invasivo foi muito boa. CONCLUSÕES: A capacidade de invadir do carcinoma in situ parece independente dos genes HER-2/neu e TP53. A aparência geral do carcinoma de mama é formulada na iniciação da carcinogênese e os genes Her-2/neu e TP53 estão envolvidos.

Metaplastic carcinoma of the breast--a rare breast tumour.

Malignant breast neoplasms consisting of mixtures of epithelial and mesenchymal elements, are a rarity. Pathogenesis of such diverse elements within obviously infiltrating carcinomas has been the subject of much controversy. After the advent of immunohistochemistry, it is now generally accepted that metaplasia of the epithelial elements of a carcinoma gives these lesions their pseudosarcomatous appearance. Hence the name metaplastic carcinoma is given to malignant breast neoplasms which show Cytokeratin positivity in both epithelial and mesenchymal elements. We recently encountered such a case, which is being presented here along with relevant review of literature.