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

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.