Qian H, Yu B, Zhou X
Department of Surgery, Shanghai Second Medical University.
Zhonghua Zhong Liu Za Zhi. 1995 Sep;17(5):332-5.
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 of p53 gene. At the same time, p53 gene product expression was studied immunohistochemically in these 18 cases in frozen sections. The expression of p53 protein was also immunohistochemically studied in formalin-fixed paraffin embedded specimens of 76 colorectal adenocarcinomas and 112 colorectal polyps. Eight out of 18 cases (44%) tested showed a variant band indicative of a mutation in exons 5-6 of p53 gene. Seven out of 8 cases (88%) with p53 gene mutations were positively stained for p53. There was no significant correlation between p53 expression and clinicopathological manifestations and prognosis. But the strongest staining was encountered in those cases with well differentiated and early stages of adenocarcinomas, while weaker staining was encountered in poorly differentiated and mucoid adenocarcinomas. p53 expression was not observed in proliferative polyps and adenomas with low grade dysplasia. The frequency of p53 expression reached 88% (P < 0.001) when adenoma showed malignant change. Among three types of adenomas, p53 expression was most frequent in villous type (P < 0.05). The frequency of p53 expression 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 transformation from benign adenoma to adenocarcinoma. p53 immunohistochemistry can be used as a surrogate marker for p53 gene mutation for early discovery of colorectal adenocarcinomas.
我们采用聚合酶链反应-单链构象多态性(PCR-SSCP)方法,分析了18例人类大肠腺癌中p53基因第5、6、7、8外显子的突变情况。同时,对这18例病例的冰冻切片进行免疫组织化学研究,检测p53基因产物的表达。此外,还对76例大肠腺癌和112例大肠息肉的福尔马林固定石蜡包埋标本进行了p53蛋白表达的免疫组织化学研究。在检测的18例病例中,有8例(44%)显示出变异条带,提示p53基因第5-6外显子存在突变。在8例p53基因突变的病例中,有7例(88%)p53呈阳性染色。p53表达与临床病理表现及预后之间无显著相关性。但在高分化和早期腺癌病例中染色最强,而在低分化和黏液腺癌中染色较弱。在增生性息肉和低级别发育异常的腺瘤中未观察到p53表达。当腺瘤发生恶变时,p53表达频率达到88%(P<0.001)。在三种类型的腺瘤中,绒毛状腺瘤p53表达最为常见(P<0.05)。腺瘤、恶变腺瘤和腺癌中p53表达频率分别为4%、88%和51%。这些结果表明,p53基因的遗传改变在良性腺瘤向腺癌的转变中起重要作用。p53免疫组织化学可作为p53基因突变的替代标志物,用于早期发现大肠腺癌。