Clinical usefulness of telomerase for the detection of colon cancer in ulcerative colitis patients

J Gastroenterol Hepatol. 2005 Oct;20(10):1578-83. doi: 10.1111/j.1440-1746.2005.03877.x.

Abstract

Background and aim: Colorectal carcinoma (CRC) is a complication of ulcerative colitis (UC). Although stool occult blood and colonoscopy are used to detect CRC in UC, these methods have drawbacks, in that bleeding is associated with UC and the underlying mucosa is irregular, making it difficult to detect dysplasia. Telomerase and its catalytic subunit, telomerase reverse transcriptase (hTERT), are specifically expressed in cancers, making them candidate markers for the early detection of cancer. We previously reported that assays of telomerase in pancreatic juice may be useful for the early detection of pancreatic cancer. The aims of our study were to determine whether assays for telomerase and TERT may be useful in the diagnosis of CRC developed in UC patients.

Methods: Luminal washings and biopsies were collected during colonoscopy in 66 patients; 34 with CRC, 21 with UC, and 11 controls. Telomerase activity was detected by telomeric repeat amplification protocol (TRAP) and hTERT mRNA was assayed by reverse transcription-polymerase chain reaction (RT-PCR).

Results: Telomerase activity was detected in biopsies from 33 of 34 (97%) CRC patients, 14 of 21 (67%) UC patients, and three of 11 (27%) normal controls. Expression of hTERT mRNA was observed in biopsies from 32 of 34 (94%) CRC patients, 12 of 21 (57%) UC patients, and five of 11 (45%) controls. In analyses of washing fluid, 21 of 34 (62%) of CRC patients were positive for telomerase, but all UC patients and controls were negative. The sensitivity of telomerase for CRC was 97% in tissues and 62% in washing fluid. The specificity of telomerase in washing fluid was 100%, whereas the specificity of telomerase or hTERT mRNA in tissues was 47% each.

Conclusions: For the detection of CRC arising in UC, telomerase and hTERT in colonic tissue showed high sensitivity, and telomerase in colonoscopic luminal washings revealed a high specificity. These might be candidate markers in clinical decision making for the diagnosis of CRC from UC.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Colitis, Ulcerative / enzymology*
  • Colitis, Ulcerative / pathology
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology
  • Colonoscopy
  • DNA-Binding Proteins / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Telomerase / analysis*
  • Telomerase / genetics
  • Therapeutic Irrigation

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • TERT protein, human
  • Telomerase