Immunohistochemical evaluation of bcl-2 protein expression in gastric adenocarcinomas

Abstract

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.

Role of the Bcl-2 Gene Family in Prostate Cancer Progression and Its Implications for Therapeutic Intervention

“…De novo expression of BcI-2 has been reported in a number of epithelial malignancies including those arising from the breast, urinary bladder, thyroid, stomach, lung, intestine, and prostate (32,34,(110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127) (118). These studies suggest a role for these antiapoptotic proteins in the progression of PC toward AI.…”

Apoptosis, cell proliferation and expression of Bcl-2 and Bax in gastric carcinomas: immunohistochemical and clinicopathological study

“…It is apparently correlated with a favourable prognosis in lung (Pezella et al, 1993) and breast cancers (Silvestrini et al, 1994), while not correlating with pT stage, lymph node status and survival in gastric carcinomas (Lauwers et al, 1995). In the latter other factors, including depth of tumour invasion, tumour differentiation, lymph node status, venous spread and whether curative or palliative surgery is performed, may play an important role in determining survival rates.…”

Prolonged cell survival enhances peritoneal dissemination of gastric cancer cells

“…Bcl-2 protein is highly expressed in the earliest precursor dysplastic lesions of gastrointestinal epithelium, as well as majority of gastric adenocarcinomas (Bronner et al, 1995). Immunohistochemical studies have failed to demonstrate a correlation between Bcl-2 expression and overall patient survival (Lauwers et al, 1995). These ®ndings imply that the detection of Bcl-2 protein alone is not likely to re¯ect anti-apoptotic activity in the cancer cells, since many other molecules, which function as either inhibitors or promoters of apoptosis, may also play crucial roles in the tumor cells and cooperatively determine their fate.…”