Expression of p27Kip1 Protein Associated with Poor Clinical Outcome in Human Gastric Cancer

ABSTRACT

PURPOSE: p27Kip1 protein is an inhibitor of cyclin-dependent kinases and is thought to be a potential prognostic indicator for numerous human cancers. We investigated the expression of p27Kip1 in gastric cancer in order to estimate its clinical utility. METHODS: Immunohistochemical assay for p27Kip1 protein was performed in 64 patients with primary gastric cancer. The correlation between p27Kip1 and clinical-biological parameters including patient survival was analyzed. RESULTS: p27Kip1 expression was suppressed in 40 (62.5%) of 64 gastric cancer patients. Expression of p27Kip1 was significantly reduced in poorly differentiated cancers (82.1%, 23/28; P=0.015) and was also reduced in tumors with a high S-phase fraction as compared with tumors showing a low S-phase fraction (86.7%, 26/30, 41.2%, 14/34; P=0.0002). In univariate analysis, the extent of the disease (P<0.001), and reduced expression of p27Kip1 (P=0.0006) were statistically significant to predict the patient's outcome, however depth of invasion (P=0.008) and pathologic stage (P=0.009) emerged as significant prognostic indicators in the multivariate analysis. CONCLUSION: The expression of p27Kip1 is closely linked with cell proliferation and differentiation of human gastric cancer. p27Kip1 appears to have potential as a prognostic marker in the management of gastric cancer patients.