胆囊良恶性病变组织中ABCG2、SFRP2、BRMS1和HPA的表达及临床病理意义

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

目的研究胆囊良恶性病变组织中三磷酸腺苷结合盒转运蛋白G2（ABCG2），分泌型Frizzled相关蛋白2（SFRP2），乳腺癌转移抑制基因1（BRMS1）和乙酰肝素酶（HPA）的表达水平及其临床病理意义。方法将108例胆囊腺癌、46例癌旁组织、15例腺瘤性息肉和35例慢性胆囊炎手术切除标本常规制作石蜡包埋切片，ABCG2、SFRP2、BRMS1和HPA染色方法均为EnVision免疫组化法。结果胆囊腺癌ABCG2和HPA表达阳性率明显高于癌旁组织、腺瘤性息肉和慢性胆囊炎（P〈0．05或P〈0．01）；胆囊腺癌SFRP2和BRMS1表达阳性率明显低于癌旁组织、腺瘤性息肉和慢性胆囊炎（P〈0．05或P〈0．01）；ABCG2和（或）HPA表达阳性及BRMS1和（或）SFRP2表达阴性的良性病例胆囊上皮均呈中至重度不典型增生。高分化腺癌、无淋巴结转移及未侵犯周围组织器官病例，ABCG2和HPA表达阳性率明显低于低分化腺癌、淋巴结转移及侵犯周围组织器官病例（P〈0．05或P〈0．01），但SFRP2和BRMS1表达则相反（P〈0．05或P〈0．01）。经Kaplan—Meier生存分析发现，ABCG2和HPA表达阳性病例术后生存期明显低于阴性表达病例（P=0．017，P=0．016），而SFRP2和BRMS1表达阳性病例术后生存期明显高于阴性表达病例（P=0．019，P=0．008）；Cox多变量回归分析显示，ABCG2和（或）HPA阳性表达以及SFRP2和（或）BRMS1阴性表达均为危险因素，是反映胆囊腺癌预后不良的重要指标。结论ABCG2、SFRP2、BRMS1和HPA表达与胆囊腺癌发生、临床生物学行为及预后有密切关系，ABCG2和（或）HPA阳性表达者及SFRP2和（或）BRMS1阴性表达者预后不良。

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 〈 O. 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.