Expression of E-cadherin is associated with squamous differentiation in squamous cell carcinomas.

E-cadherin is a cell surface molecule that mediates cell-cell adhesion in normal epithelium. Disabled or aberrant E-cadherin expression increases cell motility and promotes the transition of well-differentiated adenoma to invasive carcinoma. To evaluate whether E-cadherin could serve as a biomarker of squamous cell differentiation, we analyzed its expression by immunohistochemistry in formalin-fixed, paraffin-embedded tissue sections of 7 head and neck cancer patients, 19 lung cancer patients, 73 esophageal cancer patients, 19 skin cancer patients, and 18 cervical cancer patients. E-cadherin was expressed at very high levels (93%-100%) in adjacent or distant normal squamous epithelia. Likewise, most (75-100%) well-differentiated squamous cell carcinomas (SCCs) also expressed E-cadherin. In contrast, poorly differentiated SCCs expressed less than 40% of E-cadherin. Furthermore, immunohistochemical analysis showed that the differentiation-inducing agent, all-trans retinoic acid, can up-regulate E-cadherin expression in esophageal SCC cells in vitro. Our data demonstrated that E-cadherin expression is associated with SCC differentiation and that may serve as a squamous cell differentiation marker.