WWOX, FHIT, β-Catenin and 14-3-3 Sigma in 171 Gastric Adenocarcinomas
JB Rock, IS Hatzaras, M Bloomston, J Liu, WL Frankel. The Ohio State University, Columbus, OH
Background: Loss of Fragile Histidine triad (FHIT) and WW domain-containing oxidoreductase (WWOX) are seen in many cancers. 14-3-3 sigma prevents malignant transformation at the G2/M cell cycle checkpoint; both over-expression and loss have been associated with poor outcomes. Nuclear β-Catenin (βcat) has been linked to poor prognosis. We evaluated the correlation between these markers and survival in gastric adenocarcinoma (GAd).
Design: GAd (171) were retrieved and age, gender, tumor grade and outcome were reviewed. Tissue microarrays of tumor and benign stomach (33 controls) were stained with FHIT, WWOX, βcat, and 14-3-3 Sigma. FHIT, WWOX and 14-3-3 Sigma were graded as strongly positive (2), weakly positive (1) and negative (0). βcat was scored membranous (1), nuclear (2) or absent (0). Comparisons of groups were by 2-tailed student's t-test and contingency tables. Survival was analyzed with Kaplan-Meier time to event method and log-rank test. Spearman's correlation coefficiency, a logistic regression model, and Cox proportional hazards regression were used. Statistical significance was p <0.05.
Results: Mean age was 65.8 years with male: female ratio 1.2:1. FHIT and WWOX (p = 0.001) as well as FHIT and βcat (p = 0.01) showed significant correlations. Decreased FHIT and WWOX and expression of 14-3-3 Sigma were associated with poor differentiation with Odds Ratios of 2.9, 5.7 and 6.3 respectively; age, gender and βcat showed no association. Intact expression (2) of WWOX confers a survival benefit while increased age and poor differentiation are associated with shorter survival.
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