Background, bcl‐2 protooncogene encodes for a 26 kD protein effective in inhibiting programmed cell death (apoptosis). Its expression has been noted in lymphomas and colonic, lung, and breast carcinomas, bcl‐2 protein is believed to play a role in the gastric carcinogenic sequence where it has been demonstrated in dysplastic epithelium. To further study the role of bcl‐2 protein in gastric carcinogenesis and tumor progression, an immunohistochemical study of bcl‐2 expression in gastric adenocarcinomas and its relation to the histologic type, grade of differentiation, pT stage, lymph node status, and survival was performed. Methods. Immunohistochemical staining using monoclonal bcl‐2 protein antibody, clone 124, was performed on archival material. Results. Forty‐six of the sixty‐four adenocarcinomas (72%) showed bcl‐2 staining with immunoreactivity in 75% of the tumor or more. No specific pattern in the distribution of labeling was seen. bcl‐2 reactivity was significantly associated with adenocarcinomas of the intestinal morphotype. Forty‐five of 51 intestinal‐type tumors (88%) were immunoreactive versus only 1 of the “diffuse” tumors (7%) P = 0.001). Within the intestinal‐type adenocarcinomas, a trend of increasing prevalence of immunoreactivity with higher histologic grades was seen. No correlation between bcl‐2 expression and pT stage, lymph node status, or survival was observed. Conclusion. bcl‐2 expression in gastric adenocarcinoma appears to be associated almost exclusively with the intestinal morphotype and to some extent is more prevalent in grade 3 tumors. No correlation was noted with the pT stage, lymph node status, and survival. Inhibition of apoptosis through bcl‐2 protein expression appears to be specifically associated with promotion of intestinal‐type gastric adenocarcinoma but does not appear to be active and/or correlated with tumor progression.

Background. bcl‐2 protein encoded by the proto‐oncogene bcl‐2 confers to the cell a survival advantage by inhibiting apoptosis. Its aberrant expression has been reported in lymphomas and lung carcinoma. To determine if bcl‐2 plays a role in the gastric carcinogenic sequence, the authors studied bcl‐2 expression in gastric epithelial dysplasia (GED) and chronic atrophic gastritis with intestinal metaplasia (CAG‐IM). Methods. Immunohistochemical staining using monoclonal bcl‐2 protein antibody, clone 124, was performed on archival material. Results. bcl‐2 staining was seen in 13 of 16 GEDs (81%). The staining was heterogenous, suggesting that within the dysplastic epithelium, some cellular clones may have a survival advantage. When noted, the staining in IM was located in the proliferative zone, but some positivity could also be noted higher up along the cellular escalator. Normal gastric mucosa stained in the proliferative zone. Conclusions. The authors demonstrated that bcl‐2 expression is noted in GED as well as in the extended proliferative zone of CAG‐IM. This suggests that prolonged cell survival due to inhibition of apoptosis is instrumental in addition to increased cellular proliferation in the altered cellular homeostasis of the gastric carcinogenic sequence. Whether bcl‐2 protein aberrant expression is an independent process or inherent to immaturity of the cells produced by the increased proliferation awaits further studies. Cancer 1994; 73:2900–4.

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