Abnormal Cytoplasmic Localization of p27 (KIP) Protein Is Associated with Poor Survival in Gastric Carcinoma.
Kamaljeet Singh, Sicheng Wen, Lolie Noble, Rose Tavares, Steven F Moss, Murray Resnick. Rhode Island Hospital/Warren Alpert Medical School of Brown University, Providence
Background: The p27(Kip1) protein is a negative cell-cycle regulator and a potential tumor suppressor gene. Reduced nuclear p27(Kip1) protein expression is associated with increased mortality in gastric carcinoma. Recent studies have suggested that p27 phosphorylation-mediated cytoplasmic localization can confer a novel oncogenic role for the p27protein. We have demonstrated that H. pylori promotes cytoplasmic p27 expression and p27 phosphorylation at T157 and T198 in gastric cancer cells in vitro. Our aim was to investigate p27 protein expression in gastric carcinoma and to correlate its expression with patient outcome.
Design: Tissue microarrays were constructed for 164 cases of gastric carcinoma involving the antrum or body excluding the cardia. The extent (percentage) & intensity (0-3) of immunohistochemical p27 expression was assessed in the nucleus and cytoplasm of the tumor cells.The stage, tumor subtype and 5-year survival were noted from Hospital Cancer Registry data.
Results: Normal gastric mucosa showed only nuclear p27 expression in the lower 1/3-1/4 of the glandular crypts with no cytoplasmic p27 expression. Regression analysis identified 3 groups of p27 expression: 1) ↑ nuclear, ↓ cytoplasmic, 2) ↑ nuclear & ↑cytoplasmic, & 3) ↓ nuclear & ↑ or ↓ cytoplasmic. There was a significant difference in overall survival in these groups(p=0.033). Group 3 with ↓ nuclear p27 expression had the worst survival. Group 1 with ↑ nuclear & ↓ cytoplasmic p27 expression had the best overall survival. Group 2 with both ↑ nuclear and ↑ cytoplasmic p27 protein also had a poor survival, similar to group 3. In multivariate analysis cytoplasmic P27 expression was an independent predictor of survival.
Conclusions: Gastric carcinoma cells exhibited abnormal p27 protein expression including loss of nuclear and gain of cytoplasmic p27 protein. We confirmed that low nuclear p27 expression is associated with poor survival and demonstrated for the first time that high cytoplasmic p27 expression is also independently associated with poor survival in gastric carcinoma.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 160, Tuesday Morning