Expression of tumor suppressor gene p16(INK4) products in primary gastric cancer

Recent studies have shown that the cyclin-dependent kinase (CDK) inhibitor p27(Kip1) represents an indicator for patients' outcome in several human ma lignancies including gastric cancer. However, the clinicopathologic value o f another class of CDK inhibitor, p16(INK4), has not been determined. In a retrospective study, we examined the expression of p16(INK4) by immunohisto chemical assay of 80 samples of primary gastric cancers and their adjacent nonneoplastic mucosas. Less than 10% of nontumor gastric mucosal cells were p16(INK4) Positive, whereas the expression of p16(INK4) in gastric cancer cells varied widely from 0 to 100% (mean, 24.5%). The expression of p16(INK 4) was not seen in 11.3% (9/80) of the cancer cases, but in 65% (52/80) thi s protein was even overexpressed when compared with the nonneoplastic mucos a. A clinicopathologic survey indicated that a low or no expression of p16( INK4) was associated with poorly differentiated carcinoma (p = 0.0133), but the level of expression did not correlate with other parameters including patients' prognosis or with the expression of the pRb protein. In an effort to explore the underlying mechanism for the p16(INK4)-negative cases, a pr ospective study was also performed on 20 cases of gastric cancer to compare the level of the p16(INK4) protein with the methylation status of the p16( INK4) promoter. Gastric cancer tissues with methylation expressed significa ntly lower revels of the p16(INK4) protein (p = 0.0013) and two of them lac ked p16(INK4) expression altogether, whereas a II the cancer tissues withou t methylation expressed it. These findings suggest that the p16(INK4) prote in may be associated with differentiation of gastric cancer tissues and tha t methylation of the p16(INK4) promoter may, in part, account for the loss of p16(INK4) expression. Copyright (C) 2000 S. Karger AG, Basel