M2014 Members of the Glutathione Pathways Are Frequent Inactivated By Promoter Hypermethylation in Barrett's Adenocarcinoma

Abstract

97 formalin-fixed paraffin embedded biopsies of patients (66 males and 31 females, median age of 65 years) with RE (n=19), BE (n=24), LGD (n=17), HGD (n=16), or EAC (n=21) by immunohistochemistry. Protein expression of SOCS-2 was defined as strong positive, positive or negative if >50%, 20-50%, <20% of the epithelial cells were positive, respectively. Results: SOCS-2 mRNA expression was seen in all biopsy specimens. In patients with neoplasia, however, SOCS-2 expression was 3-5 fold lower compared to the expression levels in RE, BE, and healthy controls. No significant difference in SOCS-2 mRNA expression levels were seen in patients with LGD, HGD, and EAC. Strong positive SOCS-2 protein expression was found in 20% (11/54) of the specimens with neoplasia (LGD: 7/17, HGD: 0/16, EAC: 4/ 21) vs. 65% (28/43 p<0.001) of the specimens without neoplasia (RE: 10/19, BE: 18/24). Positive expression of SOCS-2 was detected in 28% (15/54) of the specimens with neoplasia (LGD: 2/17, HGD: 4/16, EAC: 9/21) vs. 23% (10/43) of the specimens without neoplasia (RE: 8/19, BE: 2/24), and SOCS-2 expression was negative in 52% (LGD: 8/17, HGD: 12/ 16, EAC: 8/21) vs. 12% (RE: 1/19, BE: 4/24, p<0.001), respectively. Conclusion: SOCS-2 expression is diminished in patients with BE-related neoplasia compared to patients with RE and BE, and healthy controls. This implies that SOCS-2 may serve as tumor suppressor gene in the esophagus. Although further exploration on the mechanism of SOCS-2 in BErelated neoplasia is needed, our data strongly suggest that SOCS-2 is an important target for anti-tumor therapy.