胆囊良恶性病变组织中EphA7和MTDH表达及临床意义

Expression of ephrin-A7 and metadherin and its clinicopathological significances in the benign and malignant lesions of gallbladder

目的研究胆囊良恶性病变组织中Eph基因家族A7（EphA7）和异黏蛋白（MTDH）表达水平及其临床病理意义。方法收集1996年6月至2006年6月收治的108例胆囊腺癌、46例癌旁组织、15例腺瘤性息肉和35例慢性胆囊炎患者手术切除标本常规制作石蜡包埋切片。应用EnVision免疫组化法检测其中EphA7和MTDH水平并分析其临床意义。结果胆囊腺癌EphA7和MTDH表达阳性率明显高于癌旁组织（x2EPhA7=12．65，x^2MTDH=13．00；P〈0．01）、腺瘤性息肉组织（x^2EPhA7=8．21，x^2MTDH=9．39；P〈0．01）和慢性胆囊炎组织（x^2EphA7=21．21，x^2MTDH：23．68；P〈0．01）；EphA7和（或）MTDH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、肿块最大径〈2cm、无淋巴结转移、未侵犯周围组织的病例EphA7和MTDH表达阳性率明显低于低分化、肿块最大径≥2cm（x^2EphA7=5．22，x^2MTDH=5．00；P〈0．05）、淋巴结转移（x^2EphA7=5．15，x^2MTnH=5．86；P〈0．05）和侵犯周围组织（x^2EDhA7=7．06，P〈0．01；x^2MTDH=4．13，P〈0．05）的病例；EphA7和MTDH在胆囊腺癌中表达水平呈高度一致性x^2=13．11，P〈0．01）。经Kaplan-Meier生存分析发现EphA7和MTDH表达阳性病例术后生存期明显低于阴性表达病例（PEPhA2=0．023，PMTDH=0．034）；Cox多变量回归分析显示EphA7和（或）MTDH阳性表达（PEPhA2=0．023，PMTDH=0．034）是反映胆囊腺癌预后不良的一个重要指标。结论EphA7和MTDH表达与胆囊腺癌发生、进展、临床生物学行为及预后有密切关系，EphA7和MTDH阳性表达者预后不良。

Objective To study the expression of ephrin-A7 （EphA7） and metadherin （MTDH） and their clinicopathological significances in the benign and malignant lesions of gallbladder. Methods EnVisiom immunohistochemical methods was used for determining the expressions of EphA7 and MTDH in routinely paraffin-embedded sections of surgically-resected specimens from 108 cases with gallbladder adenocarcinoma, 15 cases with adenomatous polyp and 35 cases with chronic cholecystitis treated from June 1996 to June 2006. And 46 cases of peritumoral tissues were also harvested as controls （ n = 35 ）. Results The positive expression rates of EphA7 and MTDH were significantly higher in gallbladder adenocareinoma than those in peritumoral tissues X^2 EphA7= 12.65, X^2MTDH = 13. 00 ; P 〈 0. 01 ）, adenomatous polyp （ X^2EphA7 = 8. 21, X^2MTDH = 9. 39 ; P 〈 0. O1 ） and chronic eholeeystitis （ X^2EphA7= 21. 21 , X^2MTDH = 23. 68 ; P 〈 0. 01 ） ; Moderately-or severely-atypical hyperplasia of gallbladder epitheli was found in the benign lesions with positive expression of EphA7 and/or MTDH. The positive rates of EphA7 and MTDH were significanctly lower in the cases of well-differentiated adenocarcinoma, maximal diameter of tumor 〈 2 cm, no-metastasis of lymph node, and tumor with no-invasiveness of regional tissues than those in the poorly-differentiated adenocaarcinoma （X^2EphA7 = 12. 34, X^2MTDH = 12. 80 ; P 〈 0. 01 ） , maximal diameter of tumor ≥2 cm （ X^2EphA7 = 5.22, X^2MTDH =5.00 ; P 〈 O. 05 ）, cases with metastasis of lymph node （ X^2EphA7 = 5.15, X^2MTDH = 5. 86 ; P〈0.05） and cases with invasiveness of regional tissues （X^2EphA7 =7.06, P 〈0. Ol; X^2MTDH =4. 13; P〈 O. 05 ） in gallbladder adenocarcinoma （ P 〈 0. 05 ）. The high consistence was found between the expressivelevels of EphA7 and MTDH in gallbladder adenocarcinoma （X^2 = 13. 11, P 〈 0. 01 ）. The univariate KaplanMeier analysis showed that the increased expression of EphA7 （ P = 0. 023 ） and MTDH （ P = 0. 034） was negatively associated with the overall survival. The multivariate Cox regression analysis showed that increased expression of EphA7 and/or MTDH （ PEphA2 = 0. 023, PMTDH =0. 034 ） was an independent poor-prognostic predictor for gallbladder adenocarcinoma. Conclusions The expression of EphA7 and/or MTDH might be closely related to the carcinogenesis, progression, clinical biological behaviors and prognosis of gallbladder adenocarcinoma. The positive expression of EphA7 and/or MTDH may predict bad-prognosis in gallbladder adenocarcinoma.