[752] Genetic Mutations in Dysplasia-Carcinoma Sequence Arising in a Background of Barrett's Esophagus – Does P53 Play a Role?

T Varma, ML Nordberg. Louisisna Health Sciences Center, Shreveport, LA; Feist-Weiller Cancer Center, Shreveport, LA

Background: Barrett's esophagus is the metaplasia of the distal esophageal lining epithelium from squamous to columnar. It usually results as a complication of prolonged gastro-esophageal reflux and is an established precursor of esophageal adenocarcinoma. Grading of dysplasia has prognostic significance and is believed to be a continuum of progressively increasing dysplasia and eventually adenocarcinoma. Several mutation sites have been suggested including P16, P53, c-myc etc.
Design: Cases of Barrett's esophagus between January 2005 and September 2009 diagnosed by light microscopy were retrieved and reviewed to include cases with no dysplasia (3), low-grade dysplasia (13) and high-grade dysplasia (5). Immunohistochemistry (IHC) for P53 and FISH (Fluorescent in-situ hybridization) analysis for Loss of Heterozygosity (LOH) at 17p13.1 (p53 gene) and abnormal copy numbers of Chromosome 17 using centromeric enumeration probe (CEP17) was done on all these cases.
Results: All cases negative for dysplasia showed a normal P53 expression on IHC and were normal on FISH. Expression of P53 was increased in five cases of low-grade dysplasia and three cases of high-grade dysplasia though LOH was observed in none of the cases by FISH. However, polysomy of chromosome 17 was seen which increased in copy numbers as the degree of dysplasia worsens, ranging on an average of 3-4 in low-grade cases to 4-12 in high-grade cases.
Conclusions: No P53 mutation is observed when site-specific probe is analyzed using FISH technology. However, polysomy of chromosome 17 is seen that increases in copy numbers when moving from low-grade to high-grade dysplasia and explains the increased protein expression detected by IHC. But P53 does not appear to be the target gene of interest that is mutated in Barrett's esophagus with dysplasia and subsequent adenocarcinoma as confirmed by FISH.
Category: Gastrointestinal

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 79, Wednesday Morning

 

Close Window