Expression of p27Kip1 and cyclin D1 proteins is inversely correlated and is associated with poor clinical outcome in human gastric cancer.

BACKGROUND AND OBJECTIVES

p27Kip1 is an inhibitor of cyclin-dependent kinases and is speculated to be a potential prognostic indicator in numerous human cancers. We investigated expression of p27Kip1 along with cyclin D1 in gastric cancer to estimate the clinical utility of p27Kip1.

METHODS

Immunohistochemical assay for p27Kip1 and cyclin D1 proteins was performed in 64 patients with primary gastric cancer. Correlation between p27Kip1 expression and clinical-biological parameters including patient survival was analyzed.

RESULTS

p27Kip1 expression was suppressed in 40 (62.5%) of 64 gastric cancer patients and cyclin D1 was overexpressed in 22 (34.4%) out of 64. Expression of p27Kip1 was significantly reduced in poorly differentiated cancers (82.1%, 23/28; P = 0.015) and was also reduced in the tumors with high S-phase fraction (86.7%, 26/30) compared with tumors showing low S-phase fraction (41.2%, 14/34; P = 0.0002). Expression of p27Kip1 and cyclin D1 was inversely correlated (P = 0.021). In univariate analysis, extent of the disease (P < 0.001), expression of cyclin D1 (P = 0.0001), and reduced expression of p27Kip1 (P = 0. 0006), were statistically significant to predict patient's outcome, but depth of invasion (P = 0.008) and pathologic stage (P = 0.009) emerged as significant prognostic indicators in multivariate analysis.

CONCLUSION

Expression of p27Kip1 is closely linked with cell proliferation and differentiation of human gastric cancer. p27Kip1 seems to have potential as a prognostic marker in the management of gastric cancer patients.