Bruner J M, Connelly J H, Saya H
Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston.
Mod Pathol. 1993 Mar;6(2):189-94.
Mutation of the p53 tumor suppressor gene is the most common genetic alteration in human tumors. The altered protein product of the mutant gene is stabilized in tumor cells and can be detected using monoclonal antibody immunohistochemistry. We report a technique for immunostaining of the altered p53 protein in routinely processed paraffin-embedded tissue sections, comparing this method with a frozen-section immunostain method for concordance. Similarly processed tumor cell lines with known mutations or deletions of the p53 gene served as positive or negative controls. The results in 25 human gliomas and 20 colorectal carcinomas showed a 100% correspondence of positive reactivity in the colorectal carcinomas and an 83% correspondence in the gliomas. In no case did the paraffin-embedded sections react in the absence of frozen section reactivity (that is, there were no false positives). Three of 18 gliomas showed reactivity in frozen sections without reactivity in the companion paraffin-embedded sections. This discrepancy could have been caused by technical factors such as length of fixation time. We propose that this new paraffin-embedded section immunostaining method will be of value as a screening technique for the investigation of p53 mutations in archived human tumors. The data thus obtained may then be correlated with clinical information and perhaps be of value in diagnosis or predicting outcome for various human cancers.
p53肿瘤抑制基因的突变是人类肿瘤中最常见的基因改变。突变基因的改变后的蛋白质产物在肿瘤细胞中稳定存在，可通过单克隆抗体免疫组织化学检测到。我们报告了一种在常规处理的石蜡包埋组织切片中对改变后的p53蛋白进行免疫染色的技术，并将该方法与冷冻切片免疫染色方法进行一致性比较。具有已知p53基因突变或缺失的经过类似处理的肿瘤细胞系用作阳性或阴性对照。25例人类胶质瘤和20例结直肠癌的结果显示，结直肠癌中阳性反应性的对应率为100%，胶质瘤中为83%。在任何情况下，石蜡包埋切片在冷冻切片无反应性时均无反应（即无假阳性）。18例胶质瘤中有3例在冷冻切片中有反应性，而在相应的石蜡包埋切片中无反应性。这种差异可能是由固定时间长短等技术因素引起的。我们认为，这种新的石蜡包埋切片免疫染色方法作为一种筛查技术，对于研究存档人类肿瘤中的p53突变将具有价值。由此获得的数据随后可与临床信息相关联，可能对各种人类癌症的诊断或预测预后具有价值。
