Colonic neoplasia in acromegaly: increased proliferation or deceased apoptosis?

Abstract

Patients with acromegaly have higher prevalence of colorectal neoplasms. The pathogenetic mechanism is still unclear and may be related to sustained increase in serum GH-IGF1. We aimed to evaluate the proliferative and apoptotic markers in samples of colonic mucosa obtained during screening colonoscopic biopsy from patients with acromegaly and study their relationship to serum IGF-1 and GH levels. The study subjects included 32 patients with acromegaly (4 female), 10 healthy controls (irritable bowel syndrome) and 10 positive controls (non-acromegalic colonic adenocarcinoma). Patients with acromegaly were divided into two groups, active disease (AD) and disease in remission (AR). Two biopsies each were obtained during colonoscopy from the right colon, transverse colon and rectosigmoid region. All the polyps were biopsied and subjected to histopathological examination. Immunohistochemistry for proliferation marker (Ki-67) and apoptotic markers (caspase-3 and TdT-Mediated dUTP Nick-End Labeling (TUNEL) was carried out in the histopathological samples. Indices of proliferation were significantly different in patients with acromegaly as compared to healthy controls. The mean Ki-67 positivity was 45.1 ± 17.7% in AD and 45.6 ± 23.1% in AR, as compared to 10 ± 5% in healthy controls. While none of the healthy controls had Ki-67 positivity beyond the lower third of crypts, among patients with acromegaly 12/32 (37.5%) had mid-third positivity (P = 0.000) and 15/32 (46.8%) had full length of crypt positively (P = 0.00). Immunostaining for caspase-3 was negative in patients with acromegaly and healthy controls. TUNEL was strongly positive in patients with colonic adenocarcinoma but not in healthy controls and patients with acromegaly. IGF-1 levels were higher in those with Ki-67 positivity in the superficial mucosa. Patients with acromegaly have increased proliferation of colonic epithelial cells. Elevated levels of serum IGF1 are associated with increase proliferation in the superficial crypt cells.