Long-term expression of fibrogenic cytokines in radiation-induced damage to the internal anal sphincter

Abstract

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-beta 1 (TGF-beta 1) 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-beta 1 and CTGF were performed.

Results: CTGF and TGF-beta 1 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-beta 1 were preferentially detected in endothelial cells, myofibroblasts and fibroblasts; in addition, there was strong immunoreactivity for TGF-beta 1, 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-beta 1 and its downstream effector CTGF.