SIRT1 Is a Useful Marker for Epithelial Dysplasia and Neoplasia in Barrett's Esophagus.
Xiaohong I Wang, Songlin Zhang, Varma Tanya, Jaiyeola Thomas. Louisiana State University Health Science Center, Shreveport
Background: Documenting the presence of epithelial dysplasia and subsequently grading the dysplasia in Barrett's esophagus are clinically significant for patient's follow-up and management. However, histological diagnosis for these lesions is often challenging to general surgical pathologists and even GI pathologists. Some biomarkers, such as p53 and alpha-methylacyl-coenzyme A racemase (AMACR), have been proven to be helpful, but they show significant overlap among these lesions. We found that SIRT1, the mammal homologue of silent information regulator 2 in budding yeasts, is overexpressed in colonic tubular adenomas. The goal of this study is to investigate the value of SIRT1 in histologically confirmed Barrett's esophagus.
Design: 20 biopsies of Barrett's esophagus without epithelial dysplasia, 11 Barrett's with low-grade dysplasia, 4 Barrett's with high-grade dysplasia, and 8 invasive adenocarcinoma were included in this study. The nuclear staining of SIRT1 was blindly reviewed and graded as 0-3 by two histopathologists, and the staining patterns were also recorded. Fisher exact test was used for the statistic analysis.
Results: Most Barrett's esophagus cases without epithelial dysplasia or low-grade dysplasia (29/31) showed weak nuclear stain at the base of the crypts, and surface epithelium was negative for SIRT1. One low-grade dysplasia showed 2+ surface epithelial nuclear staining. One Barrett's esophagus without dysplasia had 2+ surface nuclear epithelial staining, however, this patient had previous diagnosis of low-grade dysplasia one year ago. Most high-grade dysplasia and invasive adenocarcinomas cases (10/11) had 2-3+ diffuse nuclear staining including surface epithelium. One invasive carcinoma case had 1+ nuclear staining. Using 2+ nuclear staining as the cutoff value, high-grade dysplasia and carcinoma (10/11) had significant higher SIRT1 staining than Barrett's esophagus without dysplasia and low-grade dysplasia (2/31) (p=0.0001).
Conclusions: SIRT1 is overexpressed in high-grade dysplasia and invasive carcinoma and can be used for diagnosis of high-grade dysplasia. There is no significant difference of SIRT1 expression between Barrett's esophagus without dysplasia and low-grade dysplasia. A large scale study and long-term follow-up are needed to find out the significance of low-grade dysplasia with 2+ SIRT1 expressions.
Monday, February 28, 2011 1:00 PM
Poster Session II # 81, Monday Afternoon