Friis-Ottessen Mariann, De Angelis Paula M, Schjølberg Aasa R, Andersen Solveig N, Clausen Ole Petter F
Division of Diagnostics and Intervention, Department of Pathology, Oslo University Hospital, Rikshospitalet, 0424 Oslo, Norway.
Department of Pathology, University of Oslo, 0424 Oslo, Norway.
Int J Mol Med. 2014 Jun;33(6):1477-83. doi: 10.3892/ijmm.2014.1708. Epub 2014 Mar 20.
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.
长期溃疡性结肠炎（UC）是一种结肠慢性炎症性疾病。它通过一个多步骤过程与结直肠癌的发生相关，该过程包括发育异常程度的增加和DNA倍体变化。然而，并非所有UC患者即使在终生患病期间都会出现这些特征，因此患者可分为发生发育异常或癌症的进展者和未表现出此类变化的非进展者。在本研究中，通过使用过氧化物酶免疫组织化学（IHC）对一组进展型和非进展型UC结肠切除术样本进行检测，估算了端粒酶催化亚基hTERT的含量。比较了进展者和非进展者结肠黏膜中的蛋白质水平，并对进展者中不同发育异常类别与DNA倍体状态之间进行了进一步比较。与非UC对照样本相比，进展者和非进展者结肠黏膜中的hTERT水平均升高，但进展者和非进展者黏膜中的hTERT水平之间未观察到差异。在非进展者中，hTERT水平与Ki67水平在很大程度上相关。当按不同类型的结肠形态分层时，与二倍体病变相比，DNA非整倍体病变中的hTERT表达降低。我们的结果表明，hTERT蛋白表达与UC进展者结肠中的非整倍体之间存在关联，并且hTERT与Ki67之间的关联可能存在一种保护机制，可防止UC结肠黏膜内出现恶性特征。
