Kaklamanis L, Gatter K C, Mortensen N, Baigrie R J, Heryet A, Lane D P, Harris A L
Nuffield Department of Pathology, John Radcliffe Hospital, Oxford, England, United Kingdom.
Am J Pathol. 1993 Jan;142(1):87-93.
To assess the expression of p53 in premalignant lesions, we examined by immunohistochemistry benign colorectal adenomas (n = 72, measuring more than 6 mm and less than 95 mm in diameter) from patients without (group I, n = 23) or with (group II, n = 49) concurrent sporadic colorectal carcinomas. Using a panel of three monoclonal antibodies (PAb 240, PAb 421, PAb 1801) and two polyclonal antibodies (CM1, C19) immunohistological staining was demonstrated in 26% of the cases (19 of 72 adenomas, 7 of 23 from group I and 12 of 49 from group II). In the majority of the cases, p53 positive foci in the adenomas occurred in the most dysplastic areas, although focal positivity was detected in glands that were histologically normal. Expression of p53 protein was also detected in 21 of 30 (70%) colorectal carcinomas of group II. In two cases focal positive staining was observed in the polyps but not in the concurrent carcinomas. Non-neoplastic colonic mucosa and stromal lymphoid cells were negative in all cases examined. Over-expression of p53 in neoplastic tissues detected by immunocytochemistry is generally believed to correlate with the presence of mutation in the gene. This may not be an absolute rule, because in some hemopoietic malignancies, there is evidence that p53 protein may be detectable in the absence of an underlying mutation. These findings therefore represent the highest incidence in colorectal adenomas of abnormalities in the p53 protein expression, probably largely due to underlying mutations. This study also suggests that immunocytochemical demonstration of p53 protein may be a suitable method for the routine detection of subpopulations of cells which, by clonal expansion, could acquire a growth advantage within an adenoma during the neoplastic process.
为评估p53在癌前病变中的表达情况，我们采用免疫组织化学方法检查了无（I组，n = 23）或有（II组，n = 49）并发散发性结直肠癌患者的良性大肠腺瘤（n = 72，直径大于6 mm且小于95 mm）。使用一组三种单克隆抗体（PAb 240、PAb 421、PAb 1801）和两种多克隆抗体（CM1、C19），72例腺瘤中有26%（19例）呈免疫组织学染色阳性，其中I组23例中有7例，II组49例中有12例。在大多数病例中，腺瘤中的p53阳性灶出现在发育异常最严重的区域，尽管在组织学正常的腺管中也检测到了局灶性阳性。在II组的30例结直肠癌中，有21例（70%）也检测到了p53蛋白的表达。在2例病例中，息肉出现局灶性阳性染色，但并发的癌组织中未出现。在所有检查的病例中，非肿瘤性结肠黏膜和基质淋巴细胞均为阴性。免疫细胞化学检测到肿瘤组织中p53的过表达通常被认为与该基因的突变有关。但这可能并非绝对规律，因为在一些血液系统恶性肿瘤中，有证据表明在没有潜在突变的情况下也可检测到p53蛋白。因此，这些发现代表了大肠腺瘤中p53蛋白表达异常的最高发生率，可能主要是由于潜在的突变。本研究还表明，p53蛋白的免疫细胞化学检测可能是一种适合常规检测细胞亚群的方法，这些细胞通过克隆扩增在肿瘤形成过程中可能在腺瘤内获得生长优势。
