Ezrin Overexpression Is Associated with Non-Gastric Location and Inferior Disease-Free Survival in Gastrointestinal Stromal Tumors (GISTs)
Y-C Wei, C-F Li, Y-T Jin, H-Y Huang. Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Chi-Mei Foundation Medical Center, Tainan, Taiwan; College of Medicine, National Cheng Kung University, Tainan, Taiwan
Background: Ezrin, a member of ezrin-radixin-moesin family, acts as a linker protein between the cell membrane and actin cytoskeleton to integrate cell adhesion-mediated signaling. It is known to implicate tumor progression, metastatic dissemination, and adverse outcomes in several cancer types, including pediatric and adult sarcomas. Despite upregulated ezrin recently shown by cDNA expression profiling, no study has systematically evaluated the significance of ezrin expression in a large, well-characterized cohort of GISTs.
Design: Ezrin immunostain was assessable in 347 cases on tissue microarrays of primary GISTs. Among these cases, mutation variants of KIT and PDGFRA receptor tyrosine kinase (RTK) genes were confirmed in 188 cases by sequencing with or without precedent DHPLC screening and dichotomized into two prognostically different groups. Follow-up was obtained in 313 cases with a median of 57 months. Ezrin overexpression, defined as 50% of tumor cells with moderate or strong cytoplasmic staining, was correlated with disease-free survival (DSS), NIH risk level, Ki-67 labeling index (LI), and RTK genotypes, etc.
Results: Ezrin overexpression, present in 66% of GISTs, was significantly associated with the non-gastric location (p= 0.002) and decreased DFS (p=0.032, univariately). However, it was not related to NIH risk category, Ki-67 LI, RTK genotypes, and other variables. In multivariate survival analysis, ezrin overexpression remained independently predictive of adverse outcome (p=0.027, risk ratio [RR]=2.038), together with Ki-67 LI>5% (p<0.001, RR=4.044), high risk category (p<0.001, RR=3.563), and non-gastric location (p=0.006, RR=2.356).
Conclusions: Ezrin is frequently overexpressed in GISTs, especially those arising from non-gastric sites. Although it is independent of NIH risk category, cell proliferation, and RTK genotype, ezrin immunoreactivity represents a valuable prognostic marker in GISTs, suggesting a causative role in conferring an aggressive phenotype.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 90, Wednesday Morning