Expression of proliferating cell nuclear antigen in gastrointestinal tract lesions and its relationship to bcl-2 expression.

We report the relationship between proliferation as measured by the expression of proliferating cell nuclear antigen (PCNA) and the proto-oncogene bcl-2 in inflammatory and neoplastic lesions of the gastrointestinal tract and associated normal tissues. We found that (1) PCNA and bcl-2 are coexpressed in the stem cell-regenerative compartments of normal tissues but are not coexpressed in carcinomas or adjacent histologically normal epithelium, (2) there is marked heterogeneity of PCNA and bcl-2 expression in neoplastic lesions of the gastrointestinal tract, and (3) overexpression of PCNA is frequently seen in histologically inactive ulcerative colitis. We postulate (1) increased bcl-2 expression in epithelium adjacent to tumors represents an inherent change in the morphologically normal epithelium because it occurs without the corresponding high proliferative state seen in the normal crypt-regenerative compartment, (2) heterogeneity may provide a mechanistic explanation for chemotherapeutic resistance in tumors since cells having high bcl-2 but low proliferative activity would have prolonged survival and might show resistance to chemotherapeutic agents, and (3) the increased proliferative state in histologically inactive ulcerative colitis may provide a partial explanation for the increased risk of colon carcinomas in these patients.