Telomerase mRNA expression and immunohistochemical detection as a biomarker of malignant transformation in patients with inflammatory bowel disease

Gastroenterol Hepatol. 2010 Apr;33(4):288-96. doi: 10.1016/j.gastrohep.2009.12.011. Epub 2010 Mar 23.

Abstract

Background: Inflammatory bowel disease is a premalignant condition for developing colorectal cancer. Since a correlation has been suggested between telomere length, chromosomal instability and neoplastic transformation in this setting, we sought to investigate whether telomerase expression in colorectal mucosa may constitute a biomarker for malignant transformation in patients with inflammatory bowel disease.

Patients and methods: Forty-seven patients with inflammatory bowel disease with and without cancer or dysplasia were evaluated for human telomerase reverse transcriptase hTERT immunostaining in paraffin-embedded, formalin-fixed colorectal tissues. In addition, hTERT mRNA expression was assessed in fresh frozen specimens from a second set of 35 patients with inflammatory bowel disease at high or low risk for neoplastic transformation.

Results: Five out of 10 patients (50%) with colorectal cancer or high-grade dysplasia exhibited hTERT immunochemical detection in adjacent, non-transformed colonic mucosa. However, this phenomenon was also observed in non-affected mucosa of patients with either long-standing (13 out of 19 patients; 68%) or short duration (13 out of 18 patients; 72%) disease without cancer or dysplasia. On the other hand, hTERT mRNA expression in non-affected colorectal mucosa from patients at high risk for neoplastic transformation due to long-standing disease was higher than in those at low risk (7.42+/-6.43 vs. 2.87+/-1.47, respectively; p=0.006).

Conclusions: Whereas hTERT immunostaining provides equivocal results, the observation that patients at high risk for colorectal cancer because of long-standing inflammatory bowel disease overexpress hTERT mRNA in non-affected colorectal mucosa suggests its potential usefulness as a biomarker of the risk of malignant transformation.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis
  • Cell Transformation, Neoplastic / genetics*
  • Colonoscopy
  • Colorectal Neoplasms / prevention & control
  • Disease Progression
  • Enzyme Induction
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Inflammatory Bowel Diseases / enzymology*
  • Inflammatory Bowel Diseases / genetics
  • Intestinal Mucosa / enzymology*
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis*
  • Risk
  • Single-Blind Method
  • Telomerase / genetics*
  • Time Factors

Substances

  • Biomarkers
  • RNA, Messenger
  • TERT protein, human
  • Telomerase