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

AbstractOBJECTIVES:
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.
AuthorsMaki Kobayashi, Hiroshi Kawachi, Toichiro Takizawa, Keisuke Uchida, Masaki Sekine, Jiro Kumagai, Kumiko Momma, Tetsuo Nemoto, Takumi Akashi, Nobuaki Funata, Yoshinobu Eishi, Morio Koike
JournalOncology (Oncology) Vol. 71 Issue 3-4 Pg. 237-45 ( 2006) ISSN: 1423-0232 [Electronic] Switzerland
PMID17652955 (Publication Type: Journal Article)
Chemical References
  • Tumor Suppressor Protein p53
Topics
  • Carcinoma in Situ (genetics, metabolism, pathology)
  • Esophageal Neoplasms (genetics, metabolism, pathology)
  • Genes, p53
  • Humans
  • Immunohistochemistry
  • Microdissection
  • Point Mutation
  • Polymerase Chain Reaction
  • Precancerous Conditions (genetics, metabolism, pathology)
  • Tumor Suppressor Protein p53 (metabolism)

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