Endocrine Abstracts

Background: Sporadic colorectal carcinoma (CRC) is more common on the left side of the colon. Acromegaly confers an increased risk of developing CRC but with an increase of right sided disease. IGFBP-3 both regulates tissue exposure to IGF-I and also exerts cellular IGF-l independent pro-apoptotic effects. Whether variation in regional IGFBP-3 expression in the colon may explain the observed pattern of disease in both normal and acromegalic patients is unknown.
Aim: 1) To compare IGFBP-3 mRNA expression at the caecum and the rectum of patients with and without acromegaly, and (2) to confirm IGFBP-3 protein expression using immunohistochemistry (ICC).
Method: Ethics approval and informed consent were gained: 24 patients with acromegaly and 26 normals gave pinch biopsies of normal mucosa from the caecum and rectum at routine colonoscopy. Patients with neoplasia or inflammation were excluded. Total RNA was extracted and mRNA of IGFBP-3 quantitated by real time RT-PCR. ICC was performed using a specific antibody against IGFBP-3.
Results: In both normals and acromegalics there was a significant increase in IGFBP-3 expression in the rectum compared to the caecum. In acromegaly median mRNA copy number/microgram total RNA 6.4x10^-6vs. 1.1x10^-6 respectively; p less than 0.01 and in normals 5.0x10 ^-6 vs. 5.8x10 ^-6; p less than 0.0001. There were no differences between acromegalics and normals. ICC confirmed IGFBP-3 protein expression in all groups; staining was strongest in the stroma rather than the epithelium of the colon.
Conclusions: In acromegaly, the decreased expression of IGFBP-3 at the caecum combined with their elevated serum IGF-l levels may contribute to the increase in right sided colonic neoplasia. In both groups, the increased expression of IGFBP-3 in the rectum suggests an active role in controlling the local mucosal microenvironment. The increased ICC staining in the stroma suggests this is the site of production of this paracrine factor.