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Changes in the Expression of the Peroxisome Proliferator-Activated Receptor Gene in the Colonic Polyps and Colonic Mucosa of Acromegalic Patients

Departments of Endocrinology and Metabolism (F.B., F.U., F.R., D.R., S.B., C.C., M.G., E.M.) and Oncology (P.V., D.C., A.C.), University of Pisa, 56124 Pisa, Italy; Division of Endocrinology (L.B.), University of Insubria, 21100 Varese, Italy

Address all correspondence and requests for reprints to: Dr. Fausto Bogazzi, Dipartimento di Endocrinologia e Metabolismo, Università di Pisa, Ospedale di Cisanello, Via Paradisa 2, 56124 Pisa, Italy. E-mail: f.bogazzi@endoc.med.unipi.it or fbogazzi{at}hotmail.com.

Acromegalic patients have an increased prevalence of colonic neoplasms and lower peroxisome proliferator-activated receptor (PPAR) levels, the latter acting as a tumor suppressor gene. In this study we evaluated the expression of PPAR 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 PPAR 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 PPAR 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 PPAR in the polyps mucosa as untreated acromegaly or controls, supporting the concept that reduced expression of PPAR might be an early event in colonic tumorigenesis.

This work was supported in part by grants from the University of Pisa (Fondi d’Ateneo) and Ministero dell’ Istruzione, dell’ Università, della Ricerca (M.I.U.R.), Rome (to E.M.), from the University of Insubria at Varese (to L.B.), and from M.I.U.R., Rome (Project Studies on the Relationship between Fetal Microchimersim and Thyroid Autoimmune Diseases; to L.B.).

Abbreviations: APC, Adenomatous polyposis coli; PPAR, peroxisome proliferator-activated receptor .

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