Long-term Expression of Fibrogenic Cytokines in Radiation-Induced Damage to the Internal Anal Sphincter
Background: There is accumulating evidence, both quantitative and qualitative, that pelvic irradiation affects anorectal function. However, the molecular mechanisms responsible for radiation-induced damage to the anal sphincter remain unclear. Aim: To determine the expression of transforming growth factor-beta1 (TGF-beta1) and its downstream effector connective tissue growth factor (CTGF) in the anal sphincter of a patient irradiated for prostate cancer. Patient: A 82 year-old patient developed a rectal adenocarcinoma and underwent an abdomino-perineal resection (APR), four years after receiving pelvic irradiation for prostate carcinoma. Methods: Tissue sections of the anal sphincter were processed for histology. Immunostaining for TGF-beta1 and CTGF were performed. Results: CTGF and TGF-beta1 immunoreactivity was detected in the irradiated anal sphincter, and was absent in controls. Immunoreactivity for both cytokines predominated in the internal sphincter. CTGF and TGF-beta1 were preferentially detected in endothelial cells, myofibroblasts and fibroblasts; in addition, there was strong immunoreactivity for TGF-beta1, but not for CTGF in smooth muscle cells of the anal canal. Conclusion: Four years after pelvic irradiation, radiation-induced damage appeared to affect predominantly the smooth muscle layer of the anal canal. The molecular mechanisms responsible for radiation-induced fibrosis to these tissues involve prolonged activation of TGF-beta1 and its downstream effector CTGF.