EXPRESSION OF APO-1 (CD95), A MEMBER OF THE NGF TNF RECEPTOR SUPERFAMILY, IN NORMAL AND NEOPLASTIC COLON EPITHELIUM/

APO-1 is a 48-kDa cell-membrane protein identical to the Fas antigen n ow designated CD95. It is a member of the NGF/TNF receptor superfamily . Anti-APO-1 monoclonal antibody induces apoptosis in a variety of cel l types expressing this antigen. We immunohistochemically investigated APO-1 expression in normal colon mucosa, 20 adenomas, 258 colon carci nomas and 10 liver metastases and carried out in vitro studies using a panel of colon-carcinoma cell lines. Immunohistochemically, APO-1 was regularly expressed at the basolateral membrane of normal colon epith elia. In a minor fraction of colon adenomas and in 39.1% of colon carc inomas APO-1 expression was diminished and in 48.1% of carcinomas, pre dominantly of the nonmucinous type, APO-1 expression was completely ab rogated. The normal level of APO-1 in carcinomas was correlated with t he mucinous type. Reduced/lost APO-1 expression was more frequent in r ectal carcinomas. Complete loss of APO-1 was more frequent in tumors t hat had already metastasized. APO-1 expression in liver metastases ess entially corresponded to that of the primary tumors. Comparative analy sis with data from previous studies revealed that the model of APO-1 e xpression is correlated with that of HLA-A,B,C./beta(2)m, HLA-DR, HLA- D-associated invariant chain and of the secretory component. Surface e xpression of APO-1 was heterogeneous in colon-carcinoma cell lines; SW 480 expressed considerable amounts of APO-1 on all cells, while HT-29 constitutively did less so and only in a minority of cells. Surfaces d ensity of APO-1 and the fraction of positive cells in HT-29 was enhanc ed by interferon-gamma (IFN-gamma) and, additively, by tumor necrosis factor-alpha (TNF-alpha), whereas in SW480 APO-1 expression was not mo dulated by these cytokines. We conclude that neoplastic transformation of colon epithelium often leads to a loss of the physiologic, high le vel of surface APO-1 by giving rise either to a stable lack of APO-1 o r to an IFN-gamma/TNF-alpha-sensitive phenotype of inducible APO-1 exp ression. (C) 1994 Wiley-Liss, Inc.