Genomic Analysis of Esophageal Columnar Cell Metaplasia Reveals Less Frequent Changes in Non-Goblet Cell Metaplasia Than Intestinal Metaplasia
Santhoshi Bandla, Kimberley Thoms, Virginia Litle, Thomas Watson, Jeffrey Peters, Kunchang Song, Tony E Godfrey, Zhongren Zhou. University of Rochester Medical Center, Rochester, NY
Background: Gastroesophageal reflux disease (GERD) results in metaplastic changes in the esophagus from normal squamous epithelium to a columnar epithelium with (IM) or without goblet cells (NGM). While the presence of goblet cells is required in the United States for diagnosis of Barrett's esophagus (BE) and follow up surveillance, this is not the case in Japan and United Kingdom. BE/IM reportedly harbors frequent genetic alterations which are often observed in adenocarcinoma. The aim of this study is to investigate the genomic changes in NGM compared to IM and to assess if NGM is at direct risk for progression to cancer.
Design: Genomic DNA from 46 biopsies (36 patients) including 23 pure non-goblet metaplasia (NGM), 16 pure intestinal metaplasia (IM) samples, and 7 composite samples (one tissue piece is NGM and the other is IM from the same patient) were analyzed using Affymetrix SNP 6.0 arrays. Normal samples from the same patient population were used as the baseline reference. Analysis was performed with Nexus 5.0 Copy number software using SNPRank segmentation algorithm with log2 copy number thresholds for gains and losses set at +0.15 and -0.2 respectively while high level gains and homozygous loss were set at +0.5 and -0.8 respectively.
Results: IM samples display cancer associated changes including high frequency loss of FHIT (44%), CDKN2A (25%), and WWOX (19%) in addition to a low frequency gains at c-MYC (6%) and GATA6 (6%). In contrast, one sample in the NGM samples displayed changes at KRAS (4%) and CDKN2A (4%). Genomic comparisons of the composite samples with available pure NGM and/or IM samples from same patients suggest that changes at CDKN2A, FHIT, and WWOX occur in the IM portion. Results from validation studies using FISH will also be reported.
Conclusions: Results from this study so far indicate that the NGM harbors genetic changes but at a much lower frequency than that observed in IM. These findings would therefore argue that NGM is at a much lesser risk for progression to cancer compared to IM, thereby supporting the US definition of BE.
Tuesday, March 20, 2012 11:30 AM
Platform Session: Section D, Tuesday Morning