p53 Mutation analysis of low-grade dysplasia and high-grade dysplasia/carcinoma in situ of the esophagus using laser capture microdissection.

ABSTRACT

OBJECTIVES: The aim of this study was to determine the prevalence and to analyze the characteristics of p53 point mutation in esophageal intraepithelial lesions. METHODS: p53 Immunohistochemical and genetic analyses were performed on histopathologically and morphometrically diagnosed lesions. Laser capture microdissection samples were used for increased accuracy. RESULTS: Of the 70 lesions studied, 21 were high-grade dysplasia/carcinoma in situ (HGD/CIS), 21 low-grade dysplasia (LGD), 16 reactive atypical epithelia (RAE) and 12 normal epithelia (NE). Immunohistochemical staining showed p53 protein accumulation in 86% (18/21) of HGD/CIS, 81% (17/21) of LGD, and in none of RAE and NE. p53 point mutation was detected in 71% (15/21) of HGD/CIS, 67% (14/21) of LGD, but in none of RAE and NE. Of HGD/CIS and LGD with p53 protein accumulation, similar percentages had mutations 83% (15/18) and 82% (14/17), respectively. Of lesions with mutations, 72% (21/29) had mutations at hot spots such as codons 238, 248, 273 and 282. CONCLUSIONS: p53 Point mutation prevalent in HGD/CIS was also present in a large number of LGD. This is strong evidence that LGD is a neoplastic lesion and that p53 point mutation is deeply involved in esophageal carcinogenesis.