PCHK2 Is Associated with Differentiation and Survival in Gastric Adenocarcinoma
JB Rock, IS Hatzaras, M Bloomston, K Huebner, WL Frankel. The Ohio State University, Columbus, OH
Background: Checkpoint kinase 2 (Chk2) is an effector kinase central in the control of cell cycle checkpoints and associated with the p53 pathways. Phosphorylation at Thr68 (pChk2) in response to DNA damage activates Chk2 leading to autophosphorylation, transient dimerization and upregulation of kinase activity. Alterations in pChk2 have been described in several cancers and recent studies have shown the potential of its inhibitors in sensitizing tumor cells to DNA-damaging agents. Our purpose was to study the correlation between pChk2 tumor grade and survival.
Design: Gastric Adenocarcinomas (168) were retrieved and age, gender, tumor grade and outcome were reviewed. Controls were obtained from uninvolved stomach in 33 cases. Tissue microarrays with 1 mm cores were stained with the pChk2 antibody. Staining was graded as strongly positive (2), weakly positive (1) and negative (0). Comparisons were made by two-tailed student's t-test for continuous data and contingency table analysis (chi-square and Fisher's exact test) where appropriate. Survival was analyzed using the Kaplan-Meier time to even method. A logistic regression model was used to identify predictors of poor differentiation. Cox proportional hazards regression was used to evaluate predictors of survival. Statistical significance was accepted at p<0.05.
Results: Mean patient age was 65.8 years with a male to female ratio 1.2:1. Most controls were negative for pChk2 (88%) with weak positive staining noted in 4 cases. Tumors stained 2, 1 and 0 in 11 (7%), 77 (46%) and 80 (48%) cases respectively. By univariate analysis with an Odds Ratio of 9.07 (95% CI 1.13, 17.23) pChk2 was statistically associated with poor differentiation (p = 0.037); by multivariate analysis the Odds Ratio was 13.34 (95% CI 1.40, 16.75; p = 0.024). Age and gender were not associated with poor differentiation. Weak pChk2 expression conferred a significant survival benefit over strong expression (p = 0.001).
Conclusions: pChk2 is expressed in many gastric cancers and strong expression is associated with poor differentiation. Weaker expression may predict longer survival. Studies are warranted to further evaluate pChk2 for prognosis and possibly chemotherapy.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 56, Tuesday Afternoon