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黏液性结直肠癌中p53基因突变及蛋白表达频率较低。

Low frequency of p53 gene mutation and protein expression in mucinous colorectal carcinomas.

作者信息

Hanski C, Tiecke F, Hummel M, Hanski M L, Ogorek D, Rolfs A, Schmitt-Gräff A, Stein H, Riecken E O

机构信息

Department of Gastroenterology, Klinikum Benjamin Franklin der Freien Universität Berlin, Germany.

出版信息

Cancer Lett. 1996 Jun 5;103(2):163-70. doi: 10.1016/0304-3835(96)04208-5.

DOI:10.1016/0304-3835(96)04208-5
PMID:8635153
Abstract

Immunohistochemical data indicate that the frequency of p53 protein overexpression is consistently lower in the mucinous than in the non-mucinous carcinomas of the breast, ovary, pancreas and colon. This peculiar immunohistochemical behavior of the mucinous phenotype could be due to the effect of large amounts of mucus on the staining or to an actual mutation frequency difference between mucinous and non-mucinous carcinomas. This question was investigated on a group of mucinous colorectal carcinomas. DNA was extracted from paraffin sections of 16 human mucinous colorectal carcinomas and the mutation frequency was determined by sequencing of p53 exons amplified in PCR. The expression of p53 protein was determined with the avidin-biotin complex-peroxidase staining procedure and CM-1 antiserum. Twenty-five percent of the tumors, exhibited p53 protein overexpression and in 31% a mutation was detected. Concordance between the two techniques was found in 69% of tumors. Overexpression without mutation was observed in 12% and mutation without overexpression in 19%. G:C --> A:T transitions represented the most frequent lesion (80%), as previously observed in non-mucinous colorectal carcinomas. These data indicate that the mutation pattern in the p53 gene is similar in mucinous and non-mucinous colorectal carcinomas. The low frequency of p53 overexpression in the mucinous phenotype is not due to a mucus effect on the staining but is related to the low mutation frequency of p53 gene. These results lead to the hypothesis that in contrast to the nonmucinous tumors the development of the majority of colonic carcinomas with the mucinous phenotype may be independent from p53 mutations.

摘要

免疫组化数据表明,在乳腺、卵巢、胰腺和结肠的黏液性癌中,p53蛋白过表达的频率始终低于非黏液性癌。黏液性表型这种特殊的免疫组化行为可能是由于大量黏液对染色的影响,或者是黏液性癌与非黏液性癌之间实际的突变频率差异所致。对一组黏液性结直肠癌进行了该问题的研究。从16例人类黏液性结直肠癌的石蜡切片中提取DNA,并通过对聚合酶链反应(PCR)扩增的p53外显子进行测序来确定突变频率。用抗生物素蛋白-生物素复合物-过氧化物酶染色法和CM-1抗血清来测定p53蛋白的表达。25%的肿瘤表现出p53蛋白过表达,31%检测到有突变。在69%的肿瘤中发现两种技术结果一致。12%观察到过表达但无突变,19%观察到有突变但无过表达。G:C→A:T转换是最常见的病变(80%),正如之前在非黏液性结直肠癌中所观察到的。这些数据表明,黏液性和非黏液性结直肠癌中p53基因的突变模式相似。黏液性表型中p53过表达频率低并非由于黏液对染色的影响,而是与p53基因的低突变频率有关。这些结果引发了这样一种假设,即与非黏液性肿瘤相反,大多数具有黏液性表型的结肠癌的发生可能独立于p53突变。

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