Acromegalic patients have an increased prevalence of
colonic neoplasms and lower
peroxisome proliferator-activated receptor gamma (
PPARgamma) levels, the latter acting as a tumor suppressor gene. In this study we evaluated the expression of
PPARgamma in the biopsy samples of the
polyps and outside
polyps colonic mucosa from seven patients with active, untreated
acromegaly, 11 with cured disease, and 15 controls. Serum GH and
IGF-I levels were higher in patients with untreated
acromegaly than in those with
acromegaly in remission or controls (P = 0.003 and P = 0.002, respectively) The expression of
PPARgamma mRNA (mean +/- SE) was 1) mucosa outside
polyps, 24,188 +/- 3,254 transcripts in the controls, 22,432 +/- 2,006 transcripts in
acromegaly in remission, and 1,952 +/- 342 transcripts in untreated
acromegaly (P < 0.0001 vs. controls and
acromegaly in remission); and 2)
polyps mucosa, 1,554 +/- 236 transcripts in the controls, 1,112 +/- 143 in
acromegaly in remission, and 1,570 +/- 251 in untreated
acromegaly (P = NS among
polyps groups and mucosa outside
polyps of untreated
acromegaly; P < 0.0001 vs. mucosa outside
polyps of controls and
acromegaly in remission). Eighty-five percent of the cells in the mucosa outside
polyps from controls or
acromegaly in remission were positive at immunohistochemistry, at variance with 45% of the cells from
polyps mucosa from each group and from those of mucosa outside
polyps of untreated
acromegaly (P = 0.0002). In conclusion, patients with untreated
acromegaly have reduced expression of
PPARgamma in the mucosa outside
polyps, which might be reversed by curing the disease; conversely, patients with
acromegaly in remission have the same low levels of expression of
PPARgamma in the
polyps mucosa as untreated
acromegaly or controls, supporting the concept that reduced expression of
PPARgamma might be an early event in colonic
tumorigenesis.