title: Clinicopathological significance of HuR expression in gallbladder carcinoma: with special emphasis on the implications of its nuclear and cytoplasmic expression.
abstract: Gallbladder carcinoma (GBC) is a relatively rare disease which pathogenesis is less clarified. Human antigen R (HuR), a RNA-binding protein, modulates the expressions of various cancer-related proteins by stabilizing or regulating the transcription of the corresponding messenger RNA. The significance of HuR expression in a large cohort with GBCs is yet to be evaluated. In total, 164 cases of GBC were selected, and immunostaining for HuR was performed. HuR nuclear (HuR-N) expression and HuR cytoplasmic (HuR-C) expression were evaluated by using a histochemical score. The results of HuR expression were correlated with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS) in 161 patients with follow-up data. HuR-N overexpression was strongly associated with high histological grade (p = 0.001), vascular invasion (p < 0.001), and high Ki-67 labeling index (p < 0.001). HuR-C overexpression was significantly related to higher primary tumor status (p < 0.001), advanced tumor stage (p < 0.001), histological type (p = 0.006), high histological grade (p < 0.001), vascular and perineurial invasion (p < 0.001 and p = 0.002, respectively), tumor necrosis (p = 0.042), and high Ki-67 labeling index (p = 0.002). Besides, HuR-C overexpression also correlates with HuR-N overexpression (p < 0.001) and cyclin A overexpression (p = 0.026). HuR-N overexpression correlated with poor DFS (p = 0.0348) in univariate analysis, but HuR-C overexpression strongly correlated with a worse DSS and DFS in both univariate (both p < 0.0001) and multivariate (DSS, p = 0.006; DFS, p = 0.001) analyses. Subcellular localization of HuR expression correlates with different adverse phenotypes of GBC. Besides, HuR-C overexpression is an independent prognostic factor for dismal DSS and DFS, suggesting its roles in tumorigenesis or carcinogenesis and as a potential prognostic marker of GBC.
authors.affiliation: Division of General Surgery, Department of Surgery, Chi-Mei Medical Center, 901, Zhonghua Rd., Yongkang Dist., Tainan City, 710, Taiwan.
authors.forename: Ding-Ping
authors.initials: DP
authors.lastname: Sun
authors.forename: Ching-Yih
authors.initials: CY
authors.lastname: Lin
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Tian
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Lin
authors.forename: Sung-Wei
authors.initials: SW
authors.lastname: Lee
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.forename: Hao-Hsien
authors.initials: HH
authors.lastname: Lee
authors.forename: Yow-Ling
authors.initials: YL
authors.lastname: Shiue
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.forename: Peir-In
authors.initials: PI
authors.lastname: Liang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D018572:Disease-Free Survival; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005704:Gallbladder / Q000378:metabolism / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D016016:Proportional Hazards Models
chemical_list: D051959:ELAV Proteins; D019394:Ki-67 Antigen