TY - JOUR
T1 - Clinicopathological significance of HuR expression in gallbladder carcinoma
T2 - With special emphasis on the implications of its nuclear and cytoplasmic expression
AU - Sun, Ding Ping
AU - Lin, Ching Yih
AU - Tian, Yu Feng
AU - Chen, Li Tzong
AU - Lin, Li Ching
AU - Lee, Sung Wei
AU - Hsing, Chung Hsi
AU - Lee, Hao Hsien
AU - Shiue, Yow Ling
AU - Huang, Hsuan Ying
AU - Li, Chien Feng
AU - Liang, Peir In
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Gallbladder cancer
KW - HuR protein
KW - Immunohistochemistry
KW - Protein localization
UR - http://www.scopus.com/inward/record.url?scp=84884286617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884286617&partnerID=8YFLogxK
U2 - 10.1007/s13277-013-0872-2
DO - 10.1007/s13277-013-0872-2
M3 - Article
C2 - 23722602
AN - SCOPUS:84884286617
SN - 1010-4283
VL - 34
SP - 3059
EP - 3069
JO - Tumor Biology
JF - Tumor Biology
IS - 5
ER -
