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HuR cytoplasmic expression is associated with increased cyclin A expression and inferior disease‐free survival in patients with gastrointestinal stromal tumours ( GIST s)
Author(s) -
Wei YuChing,
Chou FongFu,
Li ChienFeng,
Li WeiMing,
Chen YenYang,
Lan Jui,
Li ShauHsuan,
Fang FuMin,
Hu TsungHui,
Yu ShihChen,
Eng HockLiew,
Uen YihHuei,
Tian YuFang,
Wang JuiChu,
Huang HsuanYing
Publication year - 2013
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12148
Subject(s) - tissue microarray , immunohistochemistry , biology , cancer research , stromal cell , immunostaining , pdgfra , gist , cyclin d1 , pathology , medicine , cell cycle , cancer , immunology , genetics
Aims HuR is an RNA ‐binding protein that post‐transcriptionally modulates the expression of various target genes involved in carcinogenesis, such as CCNA 2 , which encodes cyclin A . The aim of this study was to evaluate the significance of H u R expression and subcellular localization in a large cohort of gastrointestinal stromal tumours ( GIST s). Methods and results HuR immunostaining was assessable for nuclear and cytoplasmic expression in 341 cases on tissue microarrays of primary GIST s, of which 318, 296 and 193 cases were also characterized for Ki67 labelling, cyclin A immunoexpression, and KIT and PDGFRA receptor tyrosine kinase ( RTK ) genotypes, respectively. The results of H u R nuclear and cytoplasmic expression were correlated with disease‐free survival ( DFS ) and clinicopathological, immunohistochemical and RTK genotypic variables. HuR cytoplasmic expression was present in 42% of primary GIST s, and was significantly related to epithelioid histology, larger tumour size, NIH risk category, and nuclear expression of Ki67 and cyclin A . Importantly, HuR cytoplasmic expression ( P < 0.001) and cyclin A overexpression ( P < 0.001) were strongly associated with worse DFS . Both variables remained independently predictive of adverse outcome [ P = 0.020 and risk ratio ( RR ) 2.605 for cytoplasmic HuR; P = 0.026 and RR 2.763 for cyclin A ]. Conclusions HuR cytoplasmic expression not only correlates with adverse prognosticators and cyclin A overexpression, but also independently predicts worse DFS , indicating a causative role in conferring tumour aggressiveness.