The potential role of Bcl-2 expression, apoptosis and cell proliferation (Ki-67 expression) in cases of gastric carcinoma and correlation with classic prognostic factors and patient outcome

Abstract

Background: This study investigated the presence of apoptosis and proliferation in gastric cancer and assesses their possible correlation with classic prognostic markers and patients' survival.

Patients and methods: The study comprised 110 patients with gastric carcinoma who underwent gastrectomy for therapeutic reasons, and did not receive any pre- or postoperative treatment. Patients were followed up for 3.5-140 months. Thick paraffin sections (4 microm) were subjected to immunohistochemistry using anti-Bcl-2 and anti-Ki-67 antibodies and to in situ hybridization [TUNEL method-apoptotic body index (ABI)]. Morphological and immunohistochemical results were correlated with clinicopathologic parameters.

Results: Bcl-2 protein was detected in 67% of adenocarcinomas with increased expression in low-grade and early-stage tumors. Bcl-2 expression did not correlate with Ki-67 index, ABI or patients' survival. Ki-67 expression was correlated with a poorer survival rate. Apoptosis was more frequently observed in advanced stage and high-grade tumors. Cox analysis revealed that tumor stage and grade, as well as Ki-67 index, constituted independent prognostic factors.

Conclusion: This study included patients with gastric cancer none of whom received any additional pre- or post-operative treatment. Thus the prognostic value of each marker studied was not affected by additional treatments. Bcl-2 expression in advanced-stage and high-grade gastric carcinomas, indicate that Bcl-2 is involved in early stage of tumor development. Ki-67 expression constitutes an independent prognostic factor regarding the outcome of patients with gastric cancer. The positive association between apoptosis and proliferation suggests that apoptosis might reflect not only cell loss but also the proliferative activity. However, further research is required in order to determine if these markers may provide useful information for the prediction of prognosis in patients with colorectal carcinoma.