Immunophenotypic and prognostic analysis of E‐cadherin and β‐catenin expression during breast carcinogenesis and tumour progression: a comparative study with CD44

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Abstract
This study was performed to investigate whether immunohistochemical expression of E-cadherin (E-cad) and β-catenin (β-cat) in conjunction with CD44 may correlate with the clinical evolution and prognosis of breast cancer. One-hundred and forty-two routinely processed breast tissue samples including normal breast, benign lesions, in situ and invasive carcinomas were investigated. E-cad and β-cat were strongly expressed by 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 expression patterns were observed in premalignant and malignant lesions. Simultaneous lack of E-cad/β-cat expression was detected in in situ and invasive lobular carcinomas in contrast to ductal lesions, in which the differential loss of the molecules was associated with poorer differentiation, irrespective of CD44 immunophenotype. Reduced E-cad (P = 0.003), β-cat (P = 0.03) and increased CD44v4 (P = 0.05) and v7 (P = 0.007) expression were significantly associated with positive lymph node status. Decreased E-cad and lack of CD44v6 expression correlated with poor survival. There was no difference between the expression of either molecule in in situ and invasive components within the same tumour. Our results indicate that changes in E-cad, β-cat and CD44 expression occur early in breast carcinogenesis; they are involved in tumour differentiation, but events additional to their deranged expression are needed to acquire an invasive phenotype.