Expression of PTEN and p27 in Gastric Cancer andTheir Relationships with Tumor Cell Proliferation

Joo, Young Eun; Lee, Wan Sik; Park, Chang Hwan; Lee, Jae Hyuk; Kim, Hyun Soo; Choi, Sung Kyu; Rew, Jong Sun; Park, Chang Soo

Abstract

The tumor suppressor gene PTEN, localized to chromosome 10q23.3 is frequently mutated during the progression of variable human cancers. The loss of this gene is thought to play an important role in tumor cell proliferation and metastasis, due to a lack of control of the signaling pathways that mediate many cellular processes such as adhesion, migration and apoptosis. The cyclin-dependent kinase inhibitor, p27 has been suggested as a downstream target of cell cycle arrest of PTEN in various in vitro studies. In this study, we evaluated the expression of PTEN in gastric cancer and assessed its relationship to the expression of p27 and tumor cell proliferation. In this study, we conducted an immunohistochemical investigation of PTEN and p27 expression in 101 patients with gastric cancer. To assess tumor cell proliferation, Ki-67 labeling index (KI) was determined by Ki-67 immunohistochemical staining. The incidence of PTEN and p27 negative expression was 46 (45.5%) and 37 (36.6%) of 101 patients. The KI varied from 10.0% to 88.0% (mean, 48.7%). The expression of PTEN did not correlate significantly with p27 expression. There are no correlation between PTEN or p27 expression and clinicopathological parameters including patient survival. The mean KI value of PTEN negative tumors was 53.3+/-17.5, which was significantly higher than that of PTEN positive tumors (p=0.026). Although not statistically significant, the mean KI value of p27 negative tumors, with 52.2+/-18.2, tended to be higher than that of p27 positive tumors (p=0.165). Combined analysis of PTEN and p27 status showed that the mean KI in both negative tumors was significantly higher than that in both positive tumors (p=0.035). These results suggest that loss of PTEN expression may play a critical role in tumor cell proliferation of gastric cancer. However, p27 may not be a downstream target of cell cycle arrest of PTEN in gastric cancer.