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人大肠肿瘤组织p53基因突变、表达及临床意义 被引量:20

THE SIGNIFICANCE OF p53 GENE MUTATIONS AND EXPRESSIONS IN HUMAN COLORECTAL TUMORS
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摘要 应用聚合酶链反应─—单链构象多态性(PCR-SSCP)和免疫组化方法,研究了18例大肠腺癌组织p53基因的突变和表达。另对76例大肠腺癌及112例大肠息肉石蜡存档组织p53的表达进行了检测。大肠癌p53基因突变率为44%(8/18),突变发生在第5~6外显子中,88%(7/8)的突变病例p53表达阳性。p53表达与大肠癌临床病理因素及预后无关,但在早期及高分化腺癌中表达较强。增生性息肉及轻度不典型增生腺瘤p53表达阴性,腺瘤癌变中表达最高(P<0.001)。绒毛状腺瘤p53表达高(P<0.05)。大肠腺瘤、腺瘤癌变和腺癌的p53表达率分别为4%(3/71)、88%(23/26)和51%(39/76)。结果表明,p53基因突变的作用发生在良性腺瘤转变为癌的阶段。检测p53能预测腺瘤的癌变倾向,有助于早期发现大肠癌。 Abstract Using a polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP)approach we analyzed 18 human colorectal adenocarcinomas for mutations in exons 5,6,7,8 ofp53 gene.At the same time,p53 gene product expression was studied immunohistochemically inthese 18 cases in frozen sections.The expression of p53 protein was also immunohistochemicallystudied in formalin-fixed paraffin embedded specimens of 76 colorectal adenocarcinomas and 112colorectal polyps.Eight out of 18 cases(44%)tested showed a variant band indicative of a muta-tion in exons 5~6 of p53 gene.Seven out of 8 cases(88%)with p53 gene mutations were posi-tively stained for p53.There was no significant correlation between p53 expression and clinico-pathological manifestations and prognosis.But the strongest staining was encountered in thosecases with well differentiated and early stages of adenocarcinomas,while weaker staining was en-countered in poorly differentiated and mucoid adenocarcinomas.p53 expression was not observedin proliferative polyps and adenomas with low grade dysplasia.The frequency of p53 expressionreached 88%(P<0.001)when adenoma showed malignant change.Among three types of adeno-mas,p53 expression was most frequent in villous type(P<0.05).The frequency of p53 expres-sion in adenoma,adenoma with malignant change and adenocarcinoma was 4%,88%and 51%respectively.These indicate that genetic changes of p53 gene play an important role in the trans-formation from benign adenoma to adenocarcinoma.p53 immnunohistochemistry can be used as asurrogate marker for p53 gene mutation for early discovery of colorectal adenocarcinomas.
出处 《中华肿瘤杂志》 CAS CSCD 北大核心 1995年第5期332-335,I007,T001,共6页 Chinese Journal of Oncology
基金 国家"八.五"攻关基金
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