胆囊良恶性病变组织中EZH2和PTEN表达及意义

Expression of enhancer of zesle homolog 2 and phosphatase and tension homolog and its clinicopathological significance in benign and malignant lesion of gallbladder

目的:研究胆囊良恶性病变组织中果蝇Zesle基因增强子2(enhancer of zesle homolog 2,EZH2)和多种进展期肿瘤突变基因(phosphatase and tension homolog,PTEN)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,EZH2和PTEN染色方法为EnVisionTM免疫组织化学法。结果:胆囊腺癌EZH2表达阳性率明显高于癌旁组织(χ2=24.49,P<0.01)、腺瘤性息肉(χ2=11.68,P<0.01)和慢性胆囊炎(χ2=31.62,P<0.01);胆囊腺癌PTEN表达阳性率明显低于癌旁组织(χ2=20.20,P<0.01)、腺瘤性息肉(χ2=10.81,P<0.01)和慢性胆囊炎(χ2=29.83,P<0.01);EZH2表达阳性和(或)PTEN表达阴性的良性病变胆囊上皮均呈中至重度不典型增生;高分化腺癌、肿块最大径<2 cm、无淋巴结转移和未侵犯周围组织病例中,EZH2表达阳性率明显低于中分化和低分化腺癌、肿块最大径≥2 cm、淋巴结转移及侵犯周围组织病例(P<0.05或P<0.01),但PTEN表达则相反(P<0.05或P<0.01)。胆囊腺癌中EZH2表达与PTEN表达呈高度不一致性(χ2=5.24,P<0.05)。结论:EZH2和PTEN表达水平可能是反映胆囊腺癌发生、进展、生物学行为及预后的重要生物学标记物。

Objective To examine the expressive level of enhancer of zesle homolog 2 （EZH2） and phosphatase and tension homolog （FFEN）, and to explore its clinicopathological significance in benign and malignant lesion of gallbladder. Methods EnVision immunohistochemical method was used to detect the expressive levels of EZH2 and PTEN in routinely paraffin-embedded sections in the resected specimens of gallbladder adenocarcinoma （ n = 108 ） , peritumoral tissues （ n = 46）, adenomatous polyp （ n = 15 ）, and chronic cholecystitis （ n = 35 ）. Results The positive rate of EZH2 was significantly higher in gallbladder adenocarcinoma than that in peritumoral tissues （X2 =24.49,P〈0.01）, adenomatous polyp（X2 =11.68,P〈0.01）, and chronic cholecystitis （X2 =31.62, P 〈0.01 ）. The benign lesions in the positive cases of EZH2 and （or） the negative ones of PTEN showed the moderately- or severely- atypical hyperplasia of gallbladder epithelium. The positive rate of PTEN was significantly lower in gallbladder adenocarcinoma than that in peritumoral tissues（n=20.20, P〈0.01）, adenomatous polyp（X2 =10.81, P〈0.01）, and chronic cholecystitis （n = 29.83, P 〈 0.01 ）. The positive rates of EZH2 were significantly lower in the highly-differentiated adenocarcinoma, the maximal diameter of mass 〈 2 cm, non-metastasis of lymphnodes, and non-infiltration of regional tissues than those in the moderately or low-differentiated ade- nocarcinoma, the maximal diameter ≥2 cm, metastasis of lymphnode, and infiltration of regional tissues （ P 〈 0.05 or P 〈 0.01 ） . High inconsistency was found between the expression of EZH2 and PTEN in gallbladder adenocarcinoma （ P 〈 0.05 ）. Conclusion Expression of EZH2 and/or PTEN might be important biological markers in the carcinogenesis, progression, biological behaviors and prognosis of gallbladder adenocarcinoma.