DOI QR코드

DOI QR Code

Evidence for Enhanced Telomerase Activity in Barrett's Esophagus with Dysplasia and Adenocarcinoma

  • Merchant, Nipun B. (Surgery and Cancer Biology, Vanderbilt University Medical Center) ;
  • Dutta, Sudhir K. (Medicine, University of Maryland School of Medicine) ;
  • Girotra, Mohit (Department of Medicine, The Johns Hopkins University/Sinai Hospital Program in Internal Medicine) ;
  • Arora, Manish (Department of Medicine, The Johns Hopkins University/Sinai Hospital Program in Internal Medicine) ;
  • Meltzer, Stephen J. (Departments of Medicine and Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center)
  • Published : 2013.02.28

Abstract

Background: Dysplasia and adenocarcinoma developing in Barrett's esophagus (BE) are not always endoscopically identifiable. Molecular markers are needed for early recognition of these focal lesions and to identify patients at increased risk of developing adenocarcinoma. The aim of the current study was to correlate increased telomerase activity (TA) with dysplasia and adenocarcinoma occurring in the setting of BE. Materials and Methods: Esophageal mucosal biopsies were obtained from patients (N=62) who had pathologically verified BE at esophagogastroduodenoscopy (EGD). Mucosal biopsies were also obtained from the gastric fundus as controls. Based on histopathology, patients were divided into three groups: 1) BE without dysplasia (n=24); 2) BE with dysplasia (both high grade and low grade, n=13); and 3) BE with adenocarcinoma (n=25). TA was measured by a PCR-based assay (TRAPeze$^{(R)}$ ELISA Telomerase Detection Kit). Statistical analyses were performed using one-way ANOVA and post-hoc Bonferroni testing. Results: TA was significantly higher in biopsies of BE with dyplasia and BE with adenocarcinoma than in BE without dysplasia. Subgroup analyses did not reveal any significant correlations between TA and patient age, length of BE, or presence of gastritis. Conclusions: Telomerase activity in esophageal mucosal biopsies of BE may constitute a useful biomarker for the early detection of esophageal dysplasia and adenocarcinoma.

Keywords

References

  1. Avilion AA, Piatyszek MA, Gupta J, et al (1996). Human telomerase RNA and telomerase activity in immortal cell lines and tumor tissues. Cancer Res, 56, 645-50.
  2. Barclay JY, Morris A, Nwokolo CU (2005). Telomerase, hTERT and splice variants in Barrett's oesophagus and oesophageal adenocarcinoma. Eur J Gastroenterol Hepatol, 17, 221-7. https://doi.org/10.1097/00042737-200502000-00014
  3. Blackburn EH (2010). Telomeres and telomerase: the means to the end (Nobel lecture). Angew Chem Int Ed Engl, 49, 7405-21. https://doi.org/10.1002/anie.201002387
  4. Blasco MA, Rizen M, Greider CW, Hanahan D (1996). Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis. Nat Genet, 12, 200-4. https://doi.org/10.1038/ng0296-200
  5. Bodnar AG, Ouellette M, Frolkis M, et al (1998). Extension of life-span by introduction of telomerase into normal human cells. Science, 279, 349-52. https://doi.org/10.1126/science.279.5349.349
  6. Canto MI, Setrakian S, Willis J, et al (2000). Methylene blue-directed biopsies improve detection of intestinal metaplasia and dysplasia in Barrett's esophagus. Gastrointest Endosc, 51, 560-8.
  7. Clement G, Braunschweig R, Pasquier N, Bosman FT, Benhatter J (2006). Methylation of APC, TIMP3, and TERT: a new predictive marker to distinguish Barrett's oesophagus patient at risk for malignant transformation. J Pathol, 208, 100-7. https://doi.org/10.1002/path.1884
  8. Dalbagni G, Han W, Zhang ZF, et al (1997). Evaluation of the telomeric repeat amplification protocol (TRAP) assay for telomerase as a diagnostic modality in recurrent bladder cancer. Clin Cancer Res, 3, 1593-8.
  9. Falk GW, Rice TW, Goldblum JR, Richter JE (1999). Jumbo biopsy forceps protocol still misses unsuspected cancer in Barrett's esophagus with high-grade dysplasia. Gastrointest Endosc, 49, 170-6. https://doi.org/10.1016/S0016-5107(99)70482-7
  10. Feng J, Funk WD, Wang SS, et al (1995). The RNA component of human telomerase. Science (New York), 269, 1236-41. https://doi.org/10.1126/science.7544491
  11. Going JJ, Fletcher-Monaghan AJ, Neilson L, et al (2004). Zoning of mucosal phenotype, dysplasia, and telomerase activity measured by telomerase repeat assay protocol in barrett's esophagus. Neoplasia, 6, 85-92.
  12. Harley CB, Kim NW (1996). Telomerase and cancer. Important Adv Oncol, 57-67.
  13. Kim NW, Piatyszek MA, Prowse KR, et al (1994). Specific association of human telomerase activity with immortal cells and cancer. Science (New York), 266, 2011-5. https://doi.org/10.1126/science.7605428
  14. Kim NW, Wu F (1997). Advances in quantification and characterization of telomerase activity by the telomeric repeat amplification protocol (TRAP). Nucleic Acids Res, 25, 2595-7. https://doi.org/10.1093/nar/25.13.2595
  15. Levine DS, Blount PL, Rudolph RE, Reid BJ (2000). Safety of a systematic endoscopic biopsy protocol in patients with Barrett's esophagus. Am J Gastroenterol, 95, 1152-7. https://doi.org/10.1111/j.1572-0241.2000.02002.x
  16. Lord RV, Salonga D, Danenberg KD, et al (2000). Telomerase reverse transcriptase expression is increased early in the Barrett's metaplasia, dysplasia, adenocarcinoma sequence. J Gastrointest Surg, 4, 135-42. https://doi.org/10.1016/S1091-255X(00)80049-9
  17. Luna RA, Gilbert E, Hunter JG (2012). High-grade dysplasia and intramucosal adenocarcinoma in Barrett's esophagus: the role of esophagectomy in the era of endoscopic eradication therapy. Curr Opin Gastroenterol, 28, 362-9. https://doi.org/10.1097/MOG.0b013e328353e346
  18. Meyerson M, Counter CM, Eaton EN, et al (1997). hEST2, putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell, 90, 785-95. https://doi.org/10.1016/S0092-8674(00)80538-3
  19. Milind R, Attwood SE (2012). Natural history of Barrett's esophagus. World J Gastroenterol, 18, 3483-91. https://doi.org/10.3748/wjg.v18.i27.3483
  20. Morales CP, Lee EL, Shay JW (1998). In situ hybridization for the detection of telomerase RNA in the progression from Barrett's esophagus to esophageal adenocarcinoma. Cancer, 83, 652-9. https://doi.org/10.1002/(SICI)1097-0142(19980815)83:4<652::AID-CNCR4>3.0.CO;2-M
  21. Nakayama JI, Tahara H, Tahara E, et al (1998). Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. Nat Genet, 18, 65-8. https://doi.org/10.1038/ng0198-65
  22. Ngamruengphong S, Sharma VK, Das A (2009). Diagnostic yield of methylene blue chromoendoscopy for detecting specialized intestinal metaplasia and dysplasia in Barrett's esophagus: a meta-analysis. Gastrointest Endosc, 69, 1021-8. https://doi.org/10.1016/j.gie.2008.06.056
  23. Pearson AS, Chiao P, Zhang L, et al (2000). The detection of telomerase activity in patients with adenocarcinoma of the pancreas by fine needle aspiration. Int J Oncol, 17, 381-5.
  24. Shammas MA, Qazi A, Batchu RB, et al (2008). Telomere maintenance in laser capture microdissection-purified Barrett's adenocarcinoma cells and effect of telomerase inhibition in vivo. Clin Cancer Res, 14, 4971-80. https://doi.org/10.1158/1078-0432.CCR-08-0473
  25. Shammas MA, Rao MY (2011). Purification of diseased cells from Barrett's esophagus and related lesions by laser capture microdissection. Methods Mol Biol, 755, 181-7. https://doi.org/10.1007/978-1-61779-163-5_14
  26. Shay JW, Wright WE (2011). Role of telomeres and telomerase in cancer. Semin Cancer Biol, 21, 349-53 https://doi.org/10.1016/j.semcancer.2011.10.001
  27. Takubo K, Nakamura K, Izumiyama N, et al (1997). Telomerase activity in esophageal carcinoma. J Surg Oncol, 66, 88-92. https://doi.org/10.1002/(SICI)1096-9098(199710)66:2<88::AID-JSO3>3.0.CO;2-H
  28. Wang DH, Souza RF (2011). Biology of Barrett's esophagus and esophageal adenocarcinoma. Gastrointest Endosc Clin N Am, 21, 25-38 https://doi.org/10.1016/j.giec.2010.09.011
  29. Wang KK, Sampliner RE (2008). Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol, 103, 788-97 https://doi.org/10.1111/j.1572-0241.2008.01835.x
  30. Zhang WW, Klotz L (2000). Telomerase activity in needle biopsies from prostate cancer and benign prostates: the influence of sampling bias. Eur J Clin Invest, 30, 275-6. https://doi.org/10.1046/j.1365-2362.2000.00637.x
  31. Zheng PS, Iwasaka T, Zhang ZM, Pater A, Sugimori H (2000). Telomerase activity in Papanicolaou smear-negative exfoliated cervical cells and its association with lesions and oncogenic human papillomaviruses. Gyn Oncol, 77, 394-8. https://doi.org/10.1006/gyno.2000.5779

Cited by

  1. Telomere length assessment in leukocytes presents potential diagnostic value in patients with breast cancer vol.11, pp.3, 2016, https://doi.org/10.3892/ol.2016.4188