TY - JOUR
T1 - Clinical implications of p53 gene mutation in the progression of Barrett's epithelium to invasive esophageal cancer
AU - Casson, Alan G.
AU - Manolopoulos, Bill
AU - Troster, Michael
AU - Kerkvliet, Nancy
AU - O'Malley, Frances
AU - Inculet, Richard
AU - Finley, Richard
AU - Roth, Jack A.
N1 - Funding Information:
This work was supported by the J. P. Bickell Foundation, the Ontario Thoracic Societv, Victoria Ho&al Research Develonment Fund and the Departmemof Surgery Academic Enrichment Fund.
PY - 1994/1
Y1 - 1994/1
N2 - The p53 tumor suppressor gene has been implicated in human esophageal tumorigenesis, and mutations are reported in primary esophageal adenocarcinomas and associated Barrett's epithelium. To evaluate the potential clinical significance of this molecular genetic marker in the progression of Barrett's epithelium to invasive esophageal cancer, we studied 20 patients with Barrett's epithelium, 10 of whom had an associated adenocarcinoma. p53 gene mutations were screened using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis and p53 oncoprotein distribution by immunohistochemistry. Point mutations were localized to exons 5 and 7 of the p53 gene, previously recognized as "hot spots." p53 gene mutations and immunoreactivity were detected in 7 of 10 patients with primary esophageal adenocarcinomas and in 6 patients with associated Barrett's epithelium, 3 of whom had high-grade dysplasia. Little correlation was observed between p53 positivity and clinicopathologic findings or outcome, although two patients with p53 mutations subsequently developed second primary cancers. Of 10 patients with Barrett's epithelium alone, 6 had p53 mutations, with mild or no dysplasia histologically, suggesting that p53 gene mutation may be an early event in progression to invasive cancer. No patient has developed invasive cancer to date, with a median follow-up of 8 years. These studies further implicate the p53 gene in the Barrett's epithelium-tocarcinoma sequence. Prospective surveillance studies incorporating molecular analysis of the p53 gene are warranted to further evaluate p53 as a predictor of patients at high risk for developing malignancy.
AB - The p53 tumor suppressor gene has been implicated in human esophageal tumorigenesis, and mutations are reported in primary esophageal adenocarcinomas and associated Barrett's epithelium. To evaluate the potential clinical significance of this molecular genetic marker in the progression of Barrett's epithelium to invasive esophageal cancer, we studied 20 patients with Barrett's epithelium, 10 of whom had an associated adenocarcinoma. p53 gene mutations were screened using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis and p53 oncoprotein distribution by immunohistochemistry. Point mutations were localized to exons 5 and 7 of the p53 gene, previously recognized as "hot spots." p53 gene mutations and immunoreactivity were detected in 7 of 10 patients with primary esophageal adenocarcinomas and in 6 patients with associated Barrett's epithelium, 3 of whom had high-grade dysplasia. Little correlation was observed between p53 positivity and clinicopathologic findings or outcome, although two patients with p53 mutations subsequently developed second primary cancers. Of 10 patients with Barrett's epithelium alone, 6 had p53 mutations, with mild or no dysplasia histologically, suggesting that p53 gene mutation may be an early event in progression to invasive cancer. No patient has developed invasive cancer to date, with a median follow-up of 8 years. These studies further implicate the p53 gene in the Barrett's epithelium-tocarcinoma sequence. Prospective surveillance studies incorporating molecular analysis of the p53 gene are warranted to further evaluate p53 as a predictor of patients at high risk for developing malignancy.
UR - http://www.scopus.com/inward/record.url?scp=0028086053&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028086053&partnerID=8YFLogxK
U2 - 10.1016/0002-9610(94)90053-1
DO - 10.1016/0002-9610(94)90053-1
M3 - Article
C2 - 8311140
AN - SCOPUS:0028086053
SN - 0002-9610
VL - 167
SP - 52
EP - 57
JO - The American Journal of Surgery
JF - The American Journal of Surgery
IS - 1
ER -