Immunophenotypic and prognostic analysis of E-cadherin and beta-catenin expression during breast carcinogenesis and tumour progression: a comparativestudy with CD44

Aims: This study was performed to investigate whether immunohistochemical e xpression of E-cadherin (E-cad) and beta-catenin (beta-cat) in conjunction with CD44 may correlate with the clinical evolution and prognosis of breast cancer. Methods and results: One-hundred and forty-two routinely processed breast t issue samples including normal breast, benign lesions, in situ and invasive carcinomas were investigated. E-cad and beta-cat were strongly expressed b y luminal and basal cells in normal glands, benign proliferative and early neoplastic intraductal lesions. Contrarily, CD44 was expressed exclusively by myoepithelial cells in normal breast, whereas different isoform expressi on patterns were observed in premalignant and malignant lesions. Simultaneo us lack of E-cad/beta-cat expression was detected in in situ and invasive l obular carcinomas in contrast to ductal lesions, in which the differential loss of the molecules was associated with poorer differentiation, irrespect ive of CD44 immunophenotype. Reduced E-cad (P = 0.003), beta-cat (P = 0.03) and increased CD44v4 (P = 0.05) and v7 (P = 0.007) expression were signifi cantly associated with positive lymph node status. Decreased E-cad and lack of CD44v6 expression correlated with poor survival. There was no differenc e between the expression of either molecule in in situ and invasive compone nts within the same tumour. Conclusions: Our results indicate that changes in E-cad, beta-cat and CD44 expression occur early in breast carcinogenesis; they are involved in tumou r differentiation, but events additional to their deranged expression are n eeded to acquire an invasive phenotype.