title: Concomitant expression of epithelial-mesenchymal transition biomarkers in breast ductal carcinoma: association with progression.
abstract: Epithelial to mesenchymal transition (EMT) is a process implicated in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. We determined the expression of some putative EMT biomarkers including E-cadherin, beta-catenin, zinc finger factor Snail (Snail), transforming growth factor beta1 (TGFbeta1), TGFbeta type II receptor (TBRII) and the HGF receptor (c-met) and their possible correlation to progression and overall survival in a series of breast ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC). Biomarkers were immunohistochemically determined in 55 IDC specimens from which 21 had lymph node metastases and in 95 DCIS specimens, 46 of these cases associated to invasive carcinoma, in a tissue microarray (TMA). Positive cytoplasmic staining of TGFbeta1 (78.2%), c-met (43.6%), Snail (34.5%), TBRII (100%), membranous E-cadherin (74.5%) and membranous/cytoplasmic beta-catenin (71%) were detected in the IDC samples. Metastatic lymph node samples displayed similar frequencies. A significant increase of c-met and TGFbeta1 positivity along DCIS to IDC progression was noted but only TGFbeta1 positivity was associated with presence of lymph node metastases and advanced stages in IDC. The evaluation of the other EMT markers in DCIS did not show differences in positivity rate as compared to invasive carcinomas. DCIS either pure or associated to IDC showed similar expression of the analyzed biomarkers. All the carcinomas exhibited positive expression of TBRII. Associations between the markers, determined by Spearman's correlation coefficient, showed a significant association between TGFbeta1 and respectively E-cadherin, beta-catenin and c-met in DCIS cases, but in invasive carcinomas only cadherin and catenin were positively correlated. Kaplan-Meier survival curves revealed that none of the EMT biomarkers analyzed were correlated with survival, which was significantly determined only by clinical and hormone receptor parameters.
authors.affiliation: Departamento de Patologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Angela Flávia
authors.initials: AF
authors.lastname: Logullo
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.forename: Fátima Solange
authors.initials: FS
authors.lastname: Pasini
authors.forename: Cynthia Aparecida Bueno De Toledo
authors.initials: CA
authors.lastname: Osório
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: M Mitzi
authors.initials: MM
authors.lastname: Brentani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D008648:Mesoderm / Q000473:pathology; D008875:Middle Aged; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor