Stopera S A, Bird R P
Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
Cytobios. 1993;73(293):73-88.
Mutation of the p53 gene is the most common genetic change accompanying the sequential development of colon cancer, but it has not been studied in the early stages of colon cancer particularly at the single and multiple crypt levels. The expression of the mutant p53 gene product in aberrant crypt foci and in adenocarcinomas induced by azoxymethane was investigated immunohistochemically, using the rat model system. Aberrant crypt foci, which may be the premalignant lesions of colon cancer, are one of the earliest recognizable lesions evident in the stepwise development of colon carcinogenesis. Immunohistochemistry was performed with three mouse monoclonal antibodies to p53 proteins. These antibodies included PAB1620 specific for the wild-type p53 protein, PAB240 specific for the mutant p53 protein and PAB421 specific for both the wild-type and mutant p53 proteins. Positive reactivity with PAB240 and PAB421 was observed in 27 of 65 (42%) aberrant crypt foci and in six of eight (75%) adenocarcinomas. No reactivity with these antibodies was present in normal adjacent crypts and in colons from untreated animals. Immunohistochemical staining with PAB240 and PAB421 was present mainly in the cytoplasm and occasionally in the nucleus of cells. This is consistent with the known preferential location of the mutant p53 protein. In adenocarcinomas, uniform staining was present throughout the tissue. Reactivity with PAB1620 in premalignant and malignant tissue was not observed. The results indicate that a p53 gene mutation occurs in aberrant crypt foci as an early genetic event in colon carcinogenesis.
p53基因的突变是结肠癌连续发展过程中最常见的基因变化，但在结肠癌的早期阶段，尤其是在单个和多个隐窝水平上尚未进行研究。利用大鼠模型系统，通过免疫组织化学方法研究了突变型p53基因产物在异常隐窝病灶和由氧化偶氮甲烷诱导的腺癌中的表达。异常隐窝病灶可能是结肠癌的癌前病变，是结肠癌发生逐步发展过程中最早可识别的病变之一。用三种针对p53蛋白的小鼠单克隆抗体进行免疫组织化学检测。这些抗体包括对野生型p53蛋白特异的PAB1620、对突变型p53蛋白特异的PAB240以及对野生型和突变型p53蛋白均特异的PAB421。在65个异常隐窝病灶中的27个（42%）以及8个腺癌中的6个（75%）观察到与PAB240和PAB421的阳性反应。在未处理动物的正常相邻隐窝和结肠中未观察到与这些抗体的反应。用PAB240和PAB421进行的免疫组织化学染色主要存在于细胞质中，偶尔存在于细胞核中。这与已知的突变型p53蛋白的优先定位一致。在腺癌中，整个组织呈现均匀染色。在癌前和恶性组织中未观察到与PAB1620的反应。结果表明，p53基因突变在异常隐窝病灶中作为结肠癌发生过程中的早期基因事件出现。
