Expression of ABCG2, SFRP2, BRMS1 and HPA in benign and malignant lesions of the gallbladder and their clinicopathological significances

Abstract

Objective To study the expression of ABCG2, SFRP2, BRMS1 and HPA and detect their clinicopathological significances in the benign and malignatnt lesions of the gallbladder.Methods EnVisiom immunohistochemical method for determining the expressions of ABCG2, SFRP2,BRMS1 and HPA was used in paraffin-embedded sections of surgical resected specimens from gallbladder adenocarcinoma (n =108), peritumoral tissues (n =46 ), adenomatous polyp (n =15 ), and chronic cholecystitis ( n =35 ).Results The positive rates of ABCG2 and HPA expression were significantly higher in gallbladder adenocarcinoma than that in peritumoral tissues, adenomatous polyp and chronic cholecystitis (P ＜ 0. 05 or P ＜ 0. 01 ) ; The positive rates of SFRP2 and BRMS1 expression were significantly lower in gallbladder adenocarcinoma than that in peritumoral tissues, adenomatous polyp and chronic cholecystitis(P ＜0. 05 or P ＜0. 01 ). The positive cases of ABCG2 and/or HPA as well as negative ones of SFRP2 and/or BRMS1 in the benign lesions showed moderately-or severely-atypical hyperplasia of gallbladder epithelium. The frequency of samples with positive staining for ABCG2 and/or HPA in cases with small tumor volume (diameter ＜ 2 cm), no lymph node metastasis, and no invasion into surrounding tissues was significantly lower than that in cases with larger tumor volume (diameter ＞ 2 cm ), lymph node metastasis, and invasion into surrounding tissues ( P ＜ 0.05 or P ＜ 0. 01 ). However, compared with ABCG2 and/or HPA, the expression of SFRP2 and/or BRMS1 showed an opposite correlation in these cases ( P ＜ 0. 05 or P ＜0. 01 ). Unitivariate Kaplan-Meier analysis showed that increased expressions of ABCG2 (P =0. 019) and HPA ( P =0. 016) or decreased expression of SFRP2 ( P =0. 019) and BRMS1 ( P =0. 008 )were associated with poorer overall survival, respectively. Multivariate Cox regression analysis showed that increased expression of ABCG2 (P =0. 018 ) and HPA ( P =0. 019) and/or decreased expression of SFRP2 (P =0. 015 ) and BRMS1 ( P =0. 011 ) were independently poor-prognostic predictors in gallbladder adenocarcinoma. Conclusions The expression of ABCG2, SFRP2, BRMS1 or HPA might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma. Key words: Gallbladder diseases; Cholecystitis; Immunohistochemsitry; Pathology, clinical; Prognosis