title: Reduced hTERT protein levels are associated with DNA aneuploidy in the colonic mucosa of patients suffering from longstanding ulcerative colitis.
abstract: Longstanding ulcerative colitis (UC) is a disease of chronic inflammation of the colon. It is associated with the development of colorectal cancer through a multistep process including increasing degrees of dysplasia and DNA-ploidy changes. However, not all UC patients will develop these characteristics even during lifelong disease, and patients may therefore be divided into progressors who develop dysplasia or cancer, and non-progressors who do not exhibit such changes. In the present study, the amount of hTERT, the catalytic subunit of the enzyme telomerase, was estimated by using peroxidase immunohistochemistry (IHC) in a set of progressor and non-progressor UC colectomies. The protein levels in the colonic mucosa of the progressors and non‑progressors were compared, and further comparisons between different categories of dysplastic development and to DNA-ploidy status within the progressors were made. Levels of hTERT were elevated in the colonic mucosa of the progressors and non-progressors when compared to non-UC control samples, but no difference was observed between the hTERT levels in the mucosa of progressors and non-progressors. The levels of hTERT associated with levels of Ki67 to a significant degree within the non-progressors. hTERT expression in lesions with DNA-aneuploidy were decreased as compared to diploid lesions, when stratified for different classes of colonic morphology. Our results indicate an association between hTERT protein expression and aneuploidy in UC-progressor colons, and also a possible protective mechanism in the association between hTERT and Ki67, against development of malignant features within the mucosa of a UC-colon.
authors.affiliation: Division of Diagnostics and Intervention, Department of Pathology, Oslo University Hospital, Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Mariann
authors.initials: M
authors.lastname: Friis-Ottessen
authors.affiliation: Division of Diagnostics and Intervention, Department of Pathology, Oslo University Hospital, Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Paula M
authors.initials: PM
authors.lastname: De Angelis
authors.affiliation: Department of Pathology, University of Oslo, 0424 Oslo, Norway.
authors.forename: Aasa R
authors.initials: AR
authors.lastname: Schjølberg
authors.affiliation: Department of Pathology, Akershus University Hospital, Division of Medicine and Laboratory Sciences, University of Oslo, 1474 Nordbyhagen, Norway.
authors.forename: Solveig N
authors.initials: SN
authors.lastname: Andersen
authors.affiliation: Division of Diagnostics and Intervention, Department of Pathology, Oslo University Hospital, Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Ole Petter F
authors.initials: OP
authors.lastname: Clausen
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D002648:Child; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019098:Telomerase