Epithelial to mesenchymal plasticity (EMP) is implicated in tumour cell invasive and metastatic capability. Basal-like breast carcinomas demonstrate the strongest evidence for EMP in breast cancer, showing highest frequency of cadherin-switching (reduced E-cadherin and activated N-cadherin expression) and the activation of mesenchymal markers (e.g. smooth muscle actin and vimentin). Invasive lobular carcinomas are very invasive and highly metastatic in some patients and consistently exhibit loss of E-cadherin. The role EMP plays in lobular tumourigenesis is controversial, but the underlying hypothesis from the analysis of small numbers of samples, is that it EMP is an unlikely phenomenon.
We have examined a series of markers of EMP in breast cancer samples showing a lobular-like growth pattern, including a large series of ILC and mixed ductal-lobular carcinomas. From a cohort of 148 ILC we observe infrequent evidence of expression of mesenchymal markers in tumour epithelial cells and little change in phenotype during progression to lymph node metastases in 37 of these cases. In 3 cases however there was concomittant expression of TWIST (nuclear localization), vimentin, smooth muscle actin and osteonectin implying a partial EMP might contribute to the invasive nature of these individual tumours. No evidence was seen for EMP in the progression of ductal to lobular like patterns of growth in mixed tumours or in a case that showed transition from a primary ductal carcinoma to a gastric metastasis exhibiting a diffuse lobular growth pattern. Snail nuclear localization was only ever evident in these cases in areas associated with necrosis.
EMP is rarely observed in clinical samples showing lobular carcinoma-like differentiation, either in classic tumours nor in promoting the transition from ductal to lobular-like growth pattern in mixed tumours. This data supports the notion that lobular carcinomas are epithelial in nature and that E-cadherin down-regulation / dysfunction occurs by other means.