HuR cytoplasmic expression is associated with increased cyclin A expression and inferior disease-free survival in patients with gastrointestinal stromal tumours (GISTs)

Yu Ching Wei, Fong Fu Chou, Chien Feng Li, Wei Ming Li, Yen Yang Chen, Jui Lan, Shau Hsuan Li, Fu Min Fang, Tsung Hui Hu, Shih Chen Yu, Hock Liew Eng, Yih Huei Uen, Yu Fang Tian, Jui Chu Wang, Hsuan Ying Huang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

7 Scopus citations

Abstract

Aims: HuR is an RNA-binding protein that post-transcriptionally modulates the expression of various target genes involved in carcinogenesis, such as CCNA2, which encodes cyclin A. The aim of this study was to evaluate the significance of HuR expression and subcellular localization in a large cohort of gastrointestinal stromal tumours (GISTs). Methods and results: HuR immunostaining was assessable for nuclear and cytoplasmic expression in 341 cases on tissue microarrays of primary GISTs, 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 HuR 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 GISTs, 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.

Original languageEnglish
Pages (from-to)445-454
Number of pages10
JournalHistopathology
Volume63
Issue number4
DOIs
StatePublished - 10 2013

Keywords

  • Cyclin A
  • GIST
  • HuR
  • Prognosis
  • Receptor tyrosine kinase

Fingerprint

Dive into the research topics of 'HuR cytoplasmic expression is associated with increased cyclin A expression and inferior disease-free survival in patients with gastrointestinal stromal tumours (GISTs)'. Together they form a unique fingerprint.

Cite this