p53 protein accumulation and gene mutations in multifocal esophageal precancerous lesions from symptom free subjects in a high incidence area for esophageal carcinoma in Henan, China
p53 protein accumulation and gene mutations in multifocal esophageal precancerous lesions from symptom free subjects in a high incidence area for esophageal carcinoma in Henan, China
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DOI：
10.1002/(sici)1097-0142(19960401)77:7
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发表时间：
1996-04-01
期刊：
影响因子：
6.2
通讯作者：
Yang, CS
中科院分区：
文献类型：
--
作者：
Wang, LD;Zhou, Q;Yang, CS
背景河南省食管癌高发区食管癌前病变和癌性病变呈多灶性。近年来的研究结果表明，p53蛋白的积累和突变发生在食管癌的发病早期。不一致的p53基因突变已被观察到在浸润性癌和浸润前病变的食管癌患者。p53在无瘤受试者的多灶性癌前病变中的改变尚未研究。从中国河南省辉县市食管癌高发区的55名无食管癌的受试者中，从每名受试者的食管的中三分之一和下三分之一各取两份活检样品。分析这些受试者中多灶性食管癌前病变中p53蛋白积聚和p53基因突变。组织病理学检查显示，110例活检组织中，20例为异型增生，72例为基底细胞增生，18例为正常上皮。2例异型增生受试者（2/55例受试者，4%）和26例基底细胞增生受试者（26/55例受试者，47%）在中下1/3活检时发生并发病变。免疫组化分析显示p53蛋白积聚的并发率较高（51/55例，93%）。对16例患者的32个样本进行p53序列分析，发现5例患者存在错义突变。在一个受试者中，在中间三分之一活检（密码子161，GCC->GAC）和下三分之一活检（密码子159，GCC->CCC）中存在不同的突变。在其他4名受试者中，在中或下三分之一活检中检测到单一突变。目前的研究结果表明，p53蛋白的积累和突变发生在人类食管癌的早期阶段。p53抑癌基因的独立体细胞突变和蛋白质在食管“场”不同区域的积累可能是多灶性食管癌发生的关键分子事件。(C)1996年美国癌症协会。
BACKGROUND. Multifocal occurrence of precancerous and cancerous lesions of the esophagus has been observed among individuals in a high incidence area for esophageal carcinoma in Henan Province, China. Results from recent studies suggest that p53 protein accumulation and mutation occur early in the pathogenesis of esophageal carcinoma. Discordant p53 gene mutations have been observed in invasive carcinoma and preinvasive lesions from a patient with esophageal carcinoma. The p53 alterations in multifocal precancerous lesions from symptom-free subjects, however, have not been investigated.METHOD. Two biopsy samples, one each from the middle-third and the lower-third of the esophagus, from each subject, were taken from 55 symptom-free subjects in a high incidence area for esophageal cancer in Huixian, Henan Province, China. p53 protein accumulation and p53 gene mutation were analyzed in multifocal esophageal precancerous lesions from these subjects.RESULTS. Histopathologic examination showed that among the 110 biopsies, 20 had dysplasia, 72 had basal cell hyperplasia, and 18 had normal epithelia. Concurrent lesions at the middle- and lower-third biopsy occurred in 2 subjects with dysplasia (2 of 55 subjects, 4%) and 26 subjects with basal cell hyperplasia (26 of 55 subjects, 47%). Analysis by immunohistochemistry showed high concurrent rates of p53 protein accumulation (51 of 55 subjects, 93%). p53 sequence analysis of 32 samples from 16 subjects identified missense mutations in 5. In one subject, there were different mutations in the middle-third biopsy (codon 161, GCC-->GAC) and the lower-third biopsy (codon 159, GCC-->CCC). A single mutation was detected in the other four subjects in either the middle- or lower-third biopsy.CONCLUSIONS. The present findings indicate that p53 protein accumulation and mutations occur in the early stages of human esophageal carcinogenesis. Independent somatic mutations of the p53 tumor suppressor gene and protein accumulation in different regions of the esophageal ''field'' might be key molecular events in multifocal esophageal carcinogenesis. (C) 1996 American Cancer Society.