Low frequency of p53 gene mutation and protein expression in mucinous colorectal carcinomas
Low frequency of p53 gene mutation and protein expression in mucinous colorectal carcinomas
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DOI：
10.1016/0304-3835(96)04208-5
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发表时间：
1996-06-05
期刊：
影响因子：
9.7
通讯作者：
Riecken, EO
中科院分区：
文献类型：
--
作者：
Hanski, C;Tiecke, F;Riecken, EO
免疫组化数据表明，p53蛋白过表达的频率始终低于粘液性比非粘液性乳腺癌，卵巢癌，胰腺癌和结肠癌。粘液性表型的这种特殊的免疫组织化学行为可能是由于大量粘液对染色的影响或粘液性和非粘液性癌之间的实际突变频率差异。本文对一组粘液性结直肠癌进行了研究。从16例粘液性结直肠癌石蜡切片中提取DNA，通过PCR扩增p53外显子序列测定其突变频率。用抗生物素蛋白-生物素复合物-过氧化物酶染色法和CM-Ⅰ抗血清检测p53蛋白的表达。25%的肿瘤表现出p53蛋白过表达，31%的肿瘤检测到突变。在69%的肿瘤中发现了两种技术之间的一致性。在12%中观察到过表达而无突变，在19%中观察到突变而无过表达。G：C --> A：T转变代表最常见的病变（80%），如先前在非粘液性结直肠癌中观察到的。这些数据表明，在p53基因的突变模式是相似的粘液性和非粘液性结直肠癌。粘液表型中p53过表达的低频率不是由于粘液对染色的影响，而是与p53基因的低突变频率有关。这些结果导致了这样的假设，即与非粘液性肿瘤相反，大多数具有粘液性表型的结肠癌的发展可能独立于p53突变。
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-I 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 non-mucinous tumors the development of the majority of colonic carcinomas with the mucinous phenotype may be independent from p53 mutations.