p53 Mutation analysis of low-grade dysplasia and high-grade dysplasia/carcinoma in situ of the esophagus using laser capture microdissection.
OBJECTIVE
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.
Kobayashi
Maki
M
Department of Pathology, Tokyo Medical and Dental University, Tokyo, Japan.
Kawachi
Hiroshi
H
Takizawa
Toichiro
T
Uchida
Keisuke
K
Sekine
Masaki
M
Kumagai
Jiro
J
Momma
Kumiko
K
Nemoto
Tetsuo
T
Akashi
Takumi
T
Funata
Nobuaki
N
Eishi
Yoshinobu
Y
Koike
Morio
M
D002278:Carcinoma in Situ / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D042282:Microdissection; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53