The products of bcl-2 and p53 genes are involved in the regulation of apoptosis and proliferation and have been associated with prognosis in several malignancies, including colorectal adenocarcinoma. Although 2 European studies have reported a prognostic significance of Bcl-2 expression in colorectal adenocarcinomas, a study from the United States did not observe such an association. Therefore, we used immunohistochemistry to evaluate the prognostic significance of Bcl-2 expression, p53 nuclear accumulation and their concomitant expression in 134 US patients with colorectal adenocarcinoma. Antigen retrieval was required for adequate detection of Bcl-2 expression. Fifty percent of the colorectal tumors were classified as expressing Bcl-2, and Bcl-2 expression was associated with longer patient survival. Antigen retrieval was not necessary for detecting nuclear accumulation of p53 by immunohistochemistry. Nuclear accumulation of p53 was detected in 44% of colorectal adenocarcinomas and was associated with decreased patient survival. Tumors that did not express detectable levels of Bcl-2 but exhibited nuclear accumulation of p53 were associated with the shortest patient survival (log rank, p 5 0.001). Multivariate Cox regression analysis demonstrated that Bcl-2 expression (p 5 0.018), p53 nuclear accumulation (p 5 0.024) and regional lymph-node metastasis (p 5 0.005) were independent prognostic factors. Although a trend toward an inverse correlation between Bcl-2 and p53 expression was observed, the prognostic value of Bcl-2 expression was independent of p53 status. Thus, assessment of both Bcl-2 and p53 status may be valuable in predicting the prognosis of patients with colorectal adenocarcinomas. Int. J. Cancer 74:346-358, 1997.r 1997 Wiley-Liss, Inc.Colorectal cancer is the most common cancer of the Western world and accounts for approx. 11% of all cancer deaths in the United States (Parker et al., 1997). As with other malignancies, colorectal adenocarcinoma is thought to develop through the accumulation of genetic alterations that dysregulate cell growth (reviewed in Fearon and Vogelstein, 1990). Two of the oncogenes that have been implicated in this process are bcl-2 and p53, the products of which are involved in apoptosis (Hockenberry et al., 1990; Yonish-Rouach et al., 1991), cell proliferation (Kobayashi et al., 1995) and tumor development (Korsmeyer, 1992).Several studies of colorectal adenocarcinomas have detected expression of Bcl-2 protein using immunohistochemistry (Hague et al., 1994;Bosari et al., 1995;Sinicrope et al., 1995;Ofner et al., 1995b;Watson et al., 1996;Baretton et al., 1996a;Flohil et al., 1996;Kaklamanis et al., 1996). Expression of Bcl-2 in colorectal cancers has been demonstrated as being a favorable prognostic factor in Austrian (Ofner et al., 1995b) and German populations (Baretton et al., 1996a; Table I). In contrast, Bosari et al. (1995) did not find a prognostic significance of Bcl-2 expression in a large US population with colorectal cancer, even though the incidence of Bcl-2-exp...

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