Tohoku J. Exp. Med., 2014 September, 234(1)

Expression of Anterior Gradient 2 Is Decreased with the Progression of Human Biliary Tract Cancer

SU JIN KIM,¹ DONG HOON KIM,² DONGCHUL KANG³ and JONG HYEOK KIM⁴

¹Department of Internal Medicine, Sejong General Hospital, Bucheon, Gyeonggi-do, Korea
²Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do, Korea
³Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Korea
⁴Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do, Korea

Biliary tract cancers include cancers of the gallbladder and extrahepatic bile ducts, and its prognosis is poor. The anterior gradient 2 (AGR2) is a protein disulfide isomerase and is highly expressed in various human cancers, such as breast, prostate and pancreas cancers. AGR2 is expressed in normal cholangiocytes and its expression is maintained during biliary carcinogenesis. However, the clinical significance of AGR2 expression in biliary tract cancer has not yet been assessed. Thus, we examined the expression of AGR2 protein in biliary tract tumors using immunohistochemistry and its association with various clinicopathologic parameters. This study included 100 patients who underwent surgery for biliary tract cancers: 46 men and 54 women with a mean and median age of 64.2 and 65.0 years, respectively. AGR2 expression was detected in ductal epithelial cells of the normal biliary tract and in 95% of biliary tract cancer tissues. While the AGR2 expression was not associated with cancer location, patient age, patient sex, degree of regional lymph node metastasis (N-status), or residual status, the AGR2 expression level was decreased with increased tumor size (T-status, p = 0.006) and progression of tumor stage (p = 0.009). Moreover, well-differentiated cancers tended to show higher AGR2 expression than poorly differentiated cancers (p = 0.068); in fact, AGR2 expression was not associated with patient survival (Kaplan-Meier analysis, p = 0.415). Thus, AGR2 is of limited value as a prognostic marker for biliary tract cancer. In conclusion, the expression of AGR2 is decreased with the progression of biliary tract cancer.

keywords —— anterior gradient 2; biliary tract cancer; clinical parameters; immunohistochemistry; prognosis

© 2014 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2014, 234, 83-88

Correspondence: Jong Hyeok Kim, M.D., Ph.D., Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang, Gyeonggi-do 431-796, Korea.

e-mail: kjh825@hallym.or.kr