Retrospective Study
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World J Gastroenterol. Jul 28, 2014; 20(28): 9564-9569
Published online Jul 28, 2014. doi: 10.3748/wjg.v20.i28.9564
Prognostic significance of nuclear hepatoma-derived growth factor expression in gallbladder cancer
Feng Tao, Min-Feng Ye, Ai-Jing Sun, Jie-Qing Lv, Guan-Gen Xu, Yuan-Ming Jing, Wei Wang
Feng Tao, Min-Feng Ye, Jie-Qing Lv, Guan-Gen Xu, Yuan-Ming Jing, Wei Wang, Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China
Ai-Jing Sun, Department of Pathology, Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang Province, China
Author contributions: Tao F and Ye MF designed the research; Lv JQ, Xu GG and Jing YM performed the experiments; Sun AJ provided vital reagents and analytical tools; Wang W analyzed the data; and Tao F wrote the manuscript.
Correspondence to: Feng Tao, MD, Professor, Chief, Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, No. 568 Zhongxing North Road, Shaoxing 312000, Zhejiang Province, China. tf_zjsx@aliyun.com
Telephone: +86-575-88229452 Fax: +86-575-85138402
Received: January 7, 2014
Revised: March 11, 2014
Accepted: April 21, 2014
Published online: July 28, 2014
Processing time: 199 Days and 17.7 Hours
Abstract

AIM: To assess the expression of nuclear hepatoma-derived growth factor (HDGF) in benign and malignant gallbladder lesions and to determine its clinicopathological significance.

METHODS: We studied 40 patients with gallbladder cancer (GBC) and a control group of 40 patients with cholelithiasis. All diagnoses of GBC and cholelithiasis were confirmed by histopathological examination after surgery. None of the patients received chemotherapy or radiotherapy before surgery. All tissue samples were fixed in 4% formalin immediately after removal and embedded in paraffin for immunohistochemical staining. The HDGF expression in the GBC and cholelithiasis specimens was examined by immunohistochemical staining. The relationship between the HDGF expression and the clinicopathological parameters of GBC was analyzed.

RESULTS: Nuclear HDGF expression was significantly higher (77.5%) in GBC than in chronic cholelithiasis (21.5%, P < 0.001). High nuclear HDGF levels were associated with histopathological subtype (P < 0.05), clinical stage (P < 0.01), and perineural invasion (P < 0.01) but not with sex, age, history of gallstones, or lymph node metastasis. A univariate Kaplan-Meier analysis showed that positive nuclear HDGF expression was associated with decreased overall survival (P < 0.01). Multivariate Cox regression analysis showed that nuclear HDGF expression and lymph node metastasis were independent risk factors for disease-free survival.

CONCLUSION: The expression of nuclear HDGF might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.

Keywords: Hepatoma-derived growth factor; Kaplan-Meier analysis; Gallbladder cancer; Immunohistochemistry

Core tip: Gallbladder cancer (GBC) is a highly invasive, rapidly proliferating tumor. Unfortunately, most conventional treatments for this tumor remain associated with poor survival. Therefore, it is necessary to identify prognostic biomarkers that are independently correlated with tumor aggressiveness. This study documents hepatoma-derived growth factor (HDGF) immunostaining in gallbladder carcinomas for the first time and shows that the expression of nuclear HDGF is closely related to the carcinogenesis, clinical biological behaviors, and prognosis of GBC.