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[人结直肠肿瘤中p53基因突变与表达的意义]

[The significance of p53 gene mutations and expressions in human colorectal tumors].

作者信息

Qian H, Yu B, Zhou X

机构信息

Department of Surgery, Shanghai Second Medical University.

出版信息

Zhonghua Zhong Liu Za Zhi. 1995 Sep;17(5):332-5.

PMID:8697968
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 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.

摘要

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。

相似文献

1
[The significance of p53 gene mutations and expressions in human colorectal tumors].[人结直肠肿瘤中p53基因突变与表达的意义]
Zhonghua Zhong Liu Za Zhi. 1995 Sep;17(5):332-5.
2
A frequent alteration of p53 gene in carcinoma in adenoma of colon.结肠腺瘤性癌中p53基因的频繁改变。
Cancer Res. 1994 Sep 1;54(17):4798-804.
3
Polymerase chain reaction-based approaches for detection of allelic loss in the p53 tumor suppressor gene in colon neoplasms.基于聚合酶链反应的方法检测结肠肿瘤中p53肿瘤抑制基因的等位基因缺失。
Am J Gastroenterol. 1997 Feb;92(2):307-12.
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p53 gene mutation and protein accumulation during neoplastic progression in Barrett's esophagus.巴雷特食管肿瘤进展过程中的p53基因突变与蛋白积聚
Mod Pathol. 2001 May;14(5):397-403. doi: 10.1038/modpathol.3880324.
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TGF-beta1 in colonic neoplasia: a genetic molecular and immunohistochemical study.转化生长因子-β1在结肠肿瘤形成中的作用:一项基因分子及免疫组织化学研究
J Exp Clin Cancer Res. 1997 Sep;16(3):281-8.
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Frequent p53 gene mutations in serrated adenomas of the colorectum.结直肠锯齿状腺瘤中频繁出现的p53基因突变。
J Pathol. 1998 Oct;186(2):131-9. doi: 10.1002/(SICI)1096-9896(1998100)186:2<131::AID-PATH158>3.0.CO;2-1.
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Telomerase activity and p53 gene mutation in familial polyposis coli.家族性腺瘤性息肉病中的端粒酶活性与p53基因突变
Anticancer Res. 2000 Sep-Oct;20(5C):3833-7.
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Immunohistochemical analysis of p53 overexpression in human colonic tumors.人结肠肿瘤中p53过表达的免疫组织化学分析
Cancer Detect Prev. 1994;18(3):187-95.
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[p53 gene mutation in cancer of the colon and rectum].[结直肠癌中的p53基因突变]
Rev Med Chil. 2000 Sep;128(9):996-1004.
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[Expression of p53 and bcl-2 in colorectal adenomas and carcinomas].[结直肠腺瘤和癌中p53与bcl-2的表达]
Medicina (B Aires). 1997;57(6):662-6.

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Co-mutation of p53, K-ras genes and accumulation of p53 protein and its correlation to clinicopathological features in rectal cancer.直肠癌中p53、K-ras基因共突变及p53蛋白积累及其与临床病理特征的相关性
World J Gastroenterol. 2004 Dec 15;10(24):3688-90. doi: 10.3748/wjg.v10.i24.3688.