Wang L D, Zhou Q, Hong J Y, Qiu S L, Yang C S
Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08854, USA.
Cancer. 1996 Apr 1;77(7):1244-9.
Multifocal occurrence of precancerous 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 the multifocal precancerous lesions from symptom-free subjects, however, have not been investigated.
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 the multifocal esophageal precancerous lesions from these subjects.
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 three 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.
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.
在中国河南省食管癌高发区的人群中，已观察到食管的癌前病变呈多灶性发生。近期研究结果表明，p53蛋白积累和突变在食管癌发病机制中早期出现。在一名食管癌患者的浸润性癌和癌前病变中观察到不一致的p53基因突变。然而，来自无症状受试者的多灶性癌前病变中的p53改变尚未得到研究。
从中国河南省辉县市食管癌高发区的55名无症状受试者中，每位受试者取自食管中下段各一个活检样本。对这些受试者多灶性食管的癌前病变进行p53蛋白积累和p53基因突变分析。
组织病理学检查显示，在110份活检样本中，20份有发育异常，72份有基底细胞增生，18份有正常上皮。中下段活检同时出现病变的情况，在2例发育异常受试者中出现（55例受试者中的2例，4%），在26例基底细胞增生受试者中出现（55例受试者中的26例，47%）。免疫组织化学分析显示p53蛋白积累的同时发生率很高（55例受试者中的51例，93%）。对16名受试者的32个样本进行p53序列分析，在5个样本中鉴定出错义突变。在一名受试者中，中下段活检有三种不同突变（密码子161，GCC→GAC）和（密码子159，GCC→CCC）。在其他四名受试者的中下段活检中检测到单个突变。
目前的研究结果表明，p53蛋白积累和突变发生在人类食管癌发生的早期阶段。p53肿瘤抑制基因的独立体细胞突变和食管“区域”不同部位的蛋白积累可能是多灶性食管癌发生的关键分子事件。
