Association of manganese superoxide dismutase expression with progression of carcinogenesis in Barrett’s Esophagus

Abstract

Abstract Introduction: There is increasing evidence that oxidative stress plays a key role in the development from Barrett's Esophagus (BE) to dysplasia to esophageal adenocarcinoma (EAC). Superoxide dismutase (SOD) catalyzes the dismutation of one of the most common oxidative stress elements, superoxide radical (O2-) to H2O2 and O2. Deficiency in the expression mitochondrial manganese (Mn) SOD, has been reported to promote carcinogenesis. The aim of our study was to evaluate MnSOD expression in a established groups of progressive BE. Methods: MnSOD immunohistochemistry was performed using rabbit polyclonal IgG and graded separately on a two-category ordinal scale in relation to the mucosa and submucosa with immunostaining assessed 0 (no staining) to 3 (strong). The total grading score of SOD immunoreactivity was the addition of mucosa and submucosa intensity, 0 (no immunoreactivity in any of the anatomic sites) to a maximum score of 6 (strong-staining reaction in each of the histoanatomic sites). Results: Ninety-two samples were evaluated for MnSOD expression. MnSOD expression was found to be significantly reduced in samples with specialized intestinal metaplasia (SIM), indefinite/low-grade dysplasia (I/LGD), high-grade dysplasia (HGD), and EAC when compared to normal esophagus (NE). MnSOD expression was similar for EAC and HGD. HistologynMnSOD expression (mean ± SD)p ValueNE173.9 ± 2.2SIM221.8 ± 1.50.002I/LGD222.2 ± 1.70.015HGD162.4 ± 1.80.043EAC152.4 ± 1.70.038 Conclusions: MnSOD Expression is significantly reduced in patients with BE and HGD and EAC. MnSOD is significantly related to the progression of BE and may represent one of the primary factors in oxidative stress protection. Further evaluation within genotypic expression and the role of anti-oxidants is needed in the effective screening and treatment of BE.