Levi E, Stryker S J, Rao M S
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Am J Gastroenterol. 1996 Jan;91(1):11-4.
Tumor development is a multistep process associated with multiple genetic alterations. Familial adenomatous polyposis (FAP) is a classical paradigm to study genetic alterations in the development of colorectal neoplasms. In this study, we investigated the timing of p53 overexpression by immunohistochemistry in colorectal carcinogenesis in FAP patients and in sporadic adenomas and adenocarcinomas.
We examined 40 microadenomas, 114 tubular adenomas, and three adenocarcinomas from five FAP patients and 30 sporadic adenomas and 14 sporadic adenocarcinomas.
p53 overexpression was observed in 43 of 114 adenomas with mild and moderate dysplasia and in three of three adenocarcinomas and in none of 40 microadenomas from FAP patients. In sporadic tumors, six of 30 adenomas with moderate to severe dysplasia and 11 of 14 carcinomas showed p53 overexpression. Uninvolved colonic mucosa in FAP patients, control patients, and patients with sporadic tumors did not stain for p53.
These results indicate that p53 overexpression occurs early in the development of colorectal adenomas in FAP, whereas it is a late event in the development of sporadic tumors.
肿瘤发展是一个与多种基因改变相关的多步骤过程。家族性腺瘤性息肉病(FAP)是研究结直肠肿瘤发生过程中基因改变的经典范例。在本研究中,我们通过免疫组织化学研究了FAP患者以及散发性腺瘤和腺癌的结直肠癌发生过程中p53过表达的时间。
我们检查了来自5例FAP患者的40个微腺瘤、114个管状腺瘤和3个腺癌,以及30个散发性腺瘤和14个散发性腺癌。
在114例伴有轻至中度发育异常的腺瘤中的43例、3例腺癌中的3例以及FAP患者的40个微腺瘤中均未观察到p53过表达。在散发性肿瘤中,30例伴有中度至重度发育异常的腺瘤中的6例以及14例癌中的11例显示p53过表达。FAP患者、对照患者和散发性肿瘤患者未受累的结肠黏膜未检测到p53染色。
这些结果表明,p53过表达在FAP患者的结直肠腺瘤发展早期出现,而在散发性肿瘤发展中是一个晚期事件。