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.