MK-1抗原和再生基因蛋白Ⅳ在胆囊良恶性病变组织中的表达及其临床意义

Expressive levels of MK-1 antigen and regenerating gene Ⅳ and its clinicopathological significance in the benign and malignant lesions of gallbladder

目的探讨胆囊良恶性病变组织中MK-1抗原（MK-1）和再生基因蛋白Ⅳ（RegⅣ）的表达水平及其临床病理意义。方法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，MK-1和RegⅣ染色方法均为EnVision免疫组织化学方法。结果胆囊腺癌MK-1和RegⅣ表达阳性率均明显高于癌旁组织（X2MK-1=18．76，P〈0．01；χ2RegⅣ=9．92，P〈0．01）、腺瘤性息肉（χ2MK-1=9．49，P〈0．01；X2RegⅣ=8．59，P〈0．01）和慢性胆囊炎（χ2MK-1=24．11，P〈0．01；χ2RegⅣ=19．24，P〈0．01）；MK-1和RegIV表达阳性的良性病例的胆囊上皮均呈中至重度不典型增生。高分化、无淋巴结转移、未侵犯周围组织的病例MK-1表达阳性率明显高于低分化、淋巴结转移和侵犯周围组织的病例（P〈0．05或P〈0．01）；高分化腺癌、无淋巴结转移和未侵犯周围组织的病例RegIV表达阳性率明显低于低分化腺癌、淋巴结转移和侵犯周围组织病例（P〈0．05或P〈0．01）。经Kaplan—Meier生存分析发现MK-1表达阳性病例术后生存期明显高于阴性表达病例（P〈0．01），但RegⅣ表达阳性病例术后生存期明显低于阴性表达病例（P〈0．01）；Cox多变量回归分析显示，MK-1阴性表达和（或）RegIV阳性表达可反映胆囊腺癌预后不良。结论MK-1和RegⅣ表达与胆囊腺癌发生、临床生物学行为及预后密切相关。

Objective To study the expression levels of MK-1 antigen and regenerating gene Ⅳ （RegⅣ） and their clinicopathologieal significance in the benign and malignant lesions of gallbladder. Methods EnVisionTM immunohistoehemical method for determining the expression of MK-1 and Reg Ⅳ was used in routinely paraffin-embedded sections of surgically reseeted specimens from gallbladder adeno- carcinoma （ n = 108 ）, peritumoral tissues （ n = 46）, adenomatous polyp （ n = 15 ）, and chronic cholecysti- tis （ n = 35 ）. Results The positive rate of MK-1 or RegⅣ expression was significantly higher in gallblad- 2 der adenocarcinoma than that in peritumoral tissues （XMK-I： 18.76,P〈0.01 ;XRosⅣ2 =9.92,P〈0.01）, adenomatous polyp（XMK-12= 9.49, P 〈 0. 01 ;XResⅣ2 = 8.59, P 〈 0. 01 ） and chronic cholecystitis （χ2MK-12 = 24. 11 ,P 〈 0. 01;XRegⅣ2 = 19.24 ,P 〈 0. 01 ）. The positive cases of MK-1 and/or Regiv in the benign le- sions showed moderate- or severe-atypical hyperplasia of gallbladder epithelia. The positive rate of MK-1 was significantly higher in the cases of well-differentiated adenocarcinoma, no-metastasis of lymph node, and no-invasiveness of regional tissues than that in the cases of low-differentiated adenocarcinoma, metasta- sis of lymph node, and invasiveness of regional tissues in gallbladder adenocarcinoma （ P 〈 0. 05 or P 〈 0. 01 ）. The positive rate of Regiv was significantly lower in the eases of well-differentiated adenocarcinoma, no-metastasis of lymph node, and no-invasiveness of regional tissues than those in the cases of low-differentiated adenocarcinoma, metastasis of lymph node, and invasiveness of regional tissues in gallbladder adenocar- cinoma （ P 〈 0. 05 or P 〈 0. 01 ）. Unitivariate Kaplan-Meier analysis revealed that the decreased expression of MK-1 （P 〈0. 01 ） or increased expression of RegIV （P 〈0. 01 ） was associated with decreased overall survival. Multivariate Cox regression analysis demonstrated that the decreased expression of MK-1 （P 〈 0.05 ） and/or increased expression of RegⅣ （P 〈 0. 01 ） was an independent bad-prognostic predictor in gallbladder adenocarcinoma. Conclusion The expression of MK-1 and/or RegiV might be closely related to the carcino- genesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.