Reduced Expression of Cyclin–dependent Kinase Inhibitor p27^Kipl Is Associated with Advanced Stage and Invasiveness of Gastric Carcinomas

Reduced expression of a cyclin-dependent kinase inhibitor p27Kip1 has recently been shown to predict poor survival of patients with breast and colorectal cancers. We studied the expression of p27Kip1 in gastric carcinomas by northern blotting, western blotting and immunohistochemistry to determine whether lack of p27 has implications for aggressiveness of gastric cancer. Reduced expression of p27 was detected in 40% of the gastric carcinomas at the mRNA level, while it was detected in 57% at the protein level. No gross alterations of the p27 gene were observed in any of the cases examined by Southern blot analysis. Immunohistochemical studies revealed that the expression of p27 was well preserved in most of the gastric adenomas, whereas it was so in only 26% of the gastric carcinomas. Fifty-six percent of the carcinomas showed almost no p27-positive cells. Decrease of p27-positive cells significantly correlated with advanced stage, depth of tumor invasion and lymph node metastasis. The expression of p27 showed an inverse correlation with the expression of cyclin E. These findings suggest that reduction of p27Kip1 protein may reflect the progression of gastric carcinomas and may be an indicator of high-grade malignancy.