Nuclear factor kappaB (NFkappaB) and cyclooxygenase-2 (Cox-2) expression in the irradiated colorectum is associated with subsequent histopathological changes.

Abstract

Recent studies have proposed that mucositis development is the same throughout the gastrointestinal tract (GIT), as it is formed from one structure embryologically. Radiation-induced oral mucositis studies have outlined the key involvement of nuclear factor kappaB (NFkappaB) and cyclooxygenase-2 (Cox-2) in its pathobiology. The purpose of this study was therefore to investigate the expression of NFkappaB and Cox-2 in the irradiated colorectum and to correlate these with the associated histopathologic changes. Colorectal tissues from 28 colorectal cancer patients treated with preoperative radiotherapy were analyzed for histopathologic changes using a variety of tissue staining methods. The expression of NFkappaB and Cox-2 in these tissues was investigated using immunohistochemistry. Changes in expression of these proteins were then correlated with the histopathologic changes. Radiation therapy caused injury to the normal colorectal tissue surrounding tumor site, particularly around the blood vessels. These changes were reflected in changes in NFkappaB and Cox-2 expression. We conclude that different regions of the GIT, the colorectum, and oral cavity have similar underlying mechanisms of radiation-induced mucositis. Understanding these mechanisms will allow new approaches to be developed to specifically target steps in the evolution of alimentary mucositis.