Topological analysis of p21(WAF1/CIP1) expression in esophageal squamous dysplasia

In the normal stratified squamous epithelium of the esophagus, only the thi rd to the fifth layers of cells express the cyclin-dependent kinase inhibit or p21(WAF1/CIP1) (p21). Using immunohistochemical staining, we examined th e topological distribution of cells expressing p21, p53, Ki67, and cytokera tin 10 (CK10), a differentiation marker of esophageal squamous cell carcino ma (SCC), in 25 superficial SCCs and 72 dysplastic lesions of the esophagus , Image analysis of p21, p53, and Ki67 expression was also performed in 48 dysplastic lesions. In superficial SCCs, although Ki67- and p53-expressing cells were mainly distributed in the deep layers of tumors despite tumor di fferentiation, the distribution of p21 correlated with tumor differentiatio n. In dysplastic lesions, p53- and Ki67-coexpressing cells tended to locate in the same layers and expand in the lower layers of epithelium with the p rogression of dysplasia. p21-expressing cells shifted to the upper Layers o f the epithelium with the progression of dysplasia, However, this change wa s heterogeneous; in some lesions, p21-expressing cells were confined to the superficial layers of atypical cells (confined type), whereas in others, p 21-overexpressing cells were scattered among atypical cells (scattered type ). CK10 expression was observed in 25% of dysplastic lesions, and the frequ ency of CK10 expression was significantly higher in the scattered than in t he confined type. Our results suggest that esophageal squamous dysplasia re presents the earliest pathological process in esophageal squamous carcinoge nesis, Our results also suggest that differentiation of esophageal SCC is d etermined at the stage of dysplasia, and that p21 plays a critical role in the differentiation process.