HuR Cytoplasmic Expression Is Predictive of Worse Disease-Free Survival in Primary Gastrointestinal Stromal Tumors (GISTs).
Tzu-Ju Chen, Chien-Feng Li, Wei-Ming Li, Yu-Ching Wei, Hsuan-Ying Huang. Kaohsiung Chang Gung Memorial Hospital, Taiwan; Chi-Mei Foundation Medical Center, Tainan, Taiwan; Kaohsiung Medical University, Taiwan
Background: As a protein of the embryonic lethal abnormal vision (ELAV) family, HuR is known to implicate in mRNA stability and turnover and mediate post-transcriptional regulation of several genes involved in carcinogenesis. In a variety of human carcinomas, HuR is highly expressed and its cytoplasmic expression correlates with poor prognosis. However, no study has systematically evaluated the expression status and subcellular localization of HuR in a large, well-characterized cohort of GISTs.
Design: HuR immunostain was performed on tissue microarrays of on tissue microarrays of primary GISTs, yielding 341 cases with assessable results. Among these, mutation variants of KIT and PDGFRA receptor tyrosine kinase (RTK) genes were determined in 193 cases by sequencing with or without precedent DHPLC screening and dichotomized into two prognostically different groups. Follow-up was obtained in 318 cases with a median of 53 months. Nuclear and cytoplasmic stains of HuR in each case were separately recorded as percentages of tumor cells with positive nuclear and/or cytoplasmic reactivity and correlated with clincopathological variables, NIH risk category, Ki-67 labeling index (LI), RTK genotypes, and disease-free survival (DFS).
Results: HuR nuclear expression was neither associated with any variable examined nor DFS. However, HuR cytoplasmic expression in ≥10% of tumor cells was present in 142 (41.7%) GISTs, which was significantly related to epithelioid histology (p=0.013), larger tumor size (p=0.031), higher NIH risk categories (p=0.001) and Ki-67 LI (p=0.008), and decreased DFS (p<0.001, univariately). However, it was not related to tumor location, RTK genotypes, and other variables. In multivariate comparisons, HuR cytoplasmic expression remained independently predictive of adverse outcome (p=0.004, risk ratio [RR]=2.975), together with high NIH risk category (p<0.001, RR=5.261), Ki-67 LI>5% (p<0.001, RR=3.615), and non-gastric location (p=0.001, RR=2.942).
Conclusions: HuR cytoplasmic expression not only correlates with adverse prognostic variables and cell proliferation but also independently portends worse clinical outcomes in GISTs, suggesting its potentiality as a valuable prognostic biomarker and the possible causative role in conferring an aggressive phenotype.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 166, Tuesday Morning