目的 探讨突变型p53与DNA拓扑异构酶Ⅱα(TopoisomeraseⅡα,TOPOⅡα)在胆囊癌前病变及腺癌中的表达特点及临床意义.方法 通过免疫组织化学方法检测胆囊腺肌瘤样增生(腺肌瘤/病,n=29)、慢性胆囊炎(n=52,对照组)、胆囊低级别上皮内瘤变(n=21)、胆囊高级别上皮内瘤变(n=19)、胆囊浸润性腺癌(n=64)中p53和TOPOⅡα的表达;分析p53和TOPOⅡα与胆囊腺癌临床病理参数的关系以及二者表达的相关性.结果 p53和TOPOⅡα在胆囊腺肌瘤样增生(腺肌瘤/病)中表达极低,而在胆囊腺癌中呈高表达(P<0.05).胆囊腺癌中p53的表达(78.12%,50/64)明显高于慢性胆囊炎(1.92%,1/52)、低级别上皮内瘤变(23.81%,5/21)和高级别上皮内瘤变(47.37%,9/19)(χ2=85.395,P<0.05);胆囊腺癌中TOPOⅡα的表达(76.56%,49/64)明显高于慢性胆囊炎(3.85%,2/52)、低级别上皮内瘤变(28.5%,6/21)和高级别上皮内瘤变(52.63%,11/19)(χ2=81.127,P<0.05).腺癌中p53、TOPOⅡα的表达:临床分期Ⅲ—Ⅳ明显高于Ⅰ—Ⅱ者(χ2=13.042,P=0.000;χ2=16.663,P<0.000),术后5年死亡明显高于生存者(χ2=8.591,P=0.003;χ2=16.154,P<0.000),低分化腺癌明显高于高、中分化腺癌(χ2=4.790,P=0.029;χ2=5.182,P=0.023);p53和TOPOⅡα在胆囊腺癌的表达呈正相关(r=0.421,P=0.001).结论 联合检测突变型p53与TOPOⅡα在胆囊良、恶性病变中有很好的鉴别诊断价值.突变型p53与TOPOⅡα可作为评估胆囊癌发展及预后的参考指标,且TOPOⅡα可作为增殖指数反映肿瘤细胞的增殖状态.%Objective To explore the expression and clinical significance of mutant p53 and DNA topoisomerase Ⅱα(TOPO Ⅱα)in precancerous lesions and adenocarcinoma of the gall-bladder.Methods The expression of p53 and TOPO Ⅱαwas detected by immunohistochemistry in 29 cases of adenomatoid hyperplasia of the gallbladder(adenomyoma/adenomyosis),52 cases of chronic cholecystitis,21 cases of low-grade intraepithelial neoplasia of the gallbladder,19 cases of high-grade intraepithelial neoplasia of the gallbladder,and 64 cases of invasive adenocarcinoma of the gallbladder.The relationships of p53 and TOPOⅡαto clinicopathological parameters of gall-bladder adenocarcinoma were analyzed.Results The p53 and TOPO Ⅱ α were minimally expressedin gallbladder adenomatoid hyperplasia,but highly expressed in gallbladder adenocarcinoma(P < 0.05).The expression rates of p53 and TOPO Ⅱ α in gallbladder adenocarcinoma(78.12%(50/64)and 76.56%(49/64),respectively)were higher than those in chronic cholecystitis(1.92%(1/52)and 3.85%(2/52),respectively),low-grade intraepithelial neoplasia(23.81%(5/21)and 28.5%(6/21),respectively)and high-grade intraepithelial neoplasia(47.37%(9/19)and 52.63%(11/19),respectively)(χ2 =85.395 andχ2 =81.127,respectively;P <0.05).Furthermore,the expression of p53 and TOPOⅡαin stage Ⅲ-Ⅳ adenocarcinoma was higher than that instage Ⅰ-Ⅱ adenocarcinoma(χ2 =13.042 andχ2 =16.663,respectively;P =0.000 and P <0.000,respectively),and that in patients died 5 years after operation was higher than that in survivors(χ2 =8.591 andχ2 =16.154,respectively;P =0.003 and P <0.000,respectively).Moreover,theexpression of p53 and TOPOⅡαin poorly differentiated adenocarcinoma was higher than that inwell to moderately differentiated adenocarcinoma(χ2 =4.790 andχ2 =5.182,respectively;P =0.029 and P =0.023,respectively).The expression of p53 was positively correlated with the expressionof TOPO Ⅱαin gallbladder adenocarcinoma(r=0.421,P =0.001).Conclusion Combineddetection of mutant p53 and TOPO Ⅱαhas a preferable value in the differential diagnosisof benign and malignant gallbladder lesions,which can be used as the reference parameters for theevaluation of progression and prognosis of gallbladder adenocarcinoma.In addition,TOPO Ⅱ αcan be used as a proliferation index to reflect the proliferative status of tumor cells.
展开▼
