Role of p53 gene mutations in human esophageal carcinogenesis: results from immunohistochemical and mutation analyses of carcinomas and nearby non-cancerous lesions

In order to characterize p53 alterations in esophageal cancer and to study their roles in carcinogenesis, we performed gene mutation and immunohistoch emical analysis on 43 surgically resected human esophageal specimens, which contain squamous cell carcinoma (SCC) and adjacent non-cancerous lesions, from a high-incidence area of Linzhou in Henan, China, A newly developed im munohisto-selective sequencing (IHSS) method was used to enrich the p53 imm unostain-positive cells for mutation analysis. p53 gene mutations were dete cted in 30 out of 43 (70%) SCC cases. Among 29 SCC cases that were stained positive for p53 protein, 25 (86%) were found to contain p53 mutations. In five cases of SCC with homogeneous p53 staining, the same mutation was obse rved in samples taken from four different positions of each tumor. In a wel l differentiated cancer nest, p53 mutation was detected in only the periphe ral p53-positive cells. In tumor areas with heterogeneous p53 staining, eit her the area stained positive for p53 had an additional mutation to the neg atively stained area or both areas lacked any detectable p53 mutation. In t he p53-positive non-cancerous lesions adjacent to cancer, p53 mutations wer e detected in seven out of 16 (47%) samples with basal cell hyperplasia (BC H), eight out of 12 (67%) samples with dysplasia (DYS), and six out of seve n (86%) samples with carcinoma in situ (CIS), All mutations found in lesion s with DYS and CIS were the same as those in the nearby SCC, In seven cases of BCH containing mutations, only three had the same mutations as the near by SCC, The results suggest that p53 mutation is an early event in esophage al carcinogenesis occurring in most of the DYS and CIS lesions, and cells w ith such mutations will progress to carcinoma, whereas the role of p53 muta tions in BCH is less clear.