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Telomerase reverse transcriptase expression is increased early in the Barrett's metaplasia, dysplasia, adenocarcinoma sequence

Lord, R V ; Salonga, D ; Danenberg, K D ; Peters, J H ; DeMeester, T R ; Johansson, J LU ; Skinner, K A ; Chandrasoma, P ; DeMeester, S R and Bremner, C G , et al. (2000) In Journal of Gastrointestinal Surgery 4(2). p.42-135
Abstract

Barrett's esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and esophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases. To identify biomarkers associated with each stage of the Barrett's process, relative mRNA expression levels of hTERT were measured using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector (TaqMan system) in Barrett's intestinal metaplasia (n = 14), Barrett's dysplasia (n = 10), Barrett's adenocarcinoma... (More)

Barrett's esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and esophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases. To identify biomarkers associated with each stage of the Barrett's process, relative mRNA expression levels of hTERT were measured using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector (TaqMan system) in Barrett's intestinal metaplasia (n = 14), Barrett's dysplasia (n = 10), Barrett's adenocarcinoma (n = 14), and matching normal squamous esophagus tissues (n = 32). hTERT expression was significantly increased at all stages of Barrett's esophagus, including the intestinal metaplasia stage, compared to normal tissues from patients without cancer (intestinal metaplasia vs. normal esophagus, P <0.0001; dysplasia, P = 0.001; adenocarcinoma, P = 0.007; all Mann-Whitney U test ). hTERT expression levels were significantly higher in adenocarcinoma tissues than in intestinal metaplasia tissues (P = 0.003), and were higher in dysplasia compared with intestinal metaplasia tissues (P = 0.056). hTERT levels were also significantly higher in histologically normal squamous esophagus tissues from cancer patients than in normal esophagus tissues from patients with no cancer (P = 0.013). Very high expression levels ([hTERT x 100: beta-actin] >20) were found only in patients with cancer. These findings suggest that telomerase activation is an important early event in the development of Barrett's esophagus and esophageal adenocarcinoma, that very high telomerase levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients with Barrett's cancer.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adenocarcinoma/enzymology, Barrett Esophagus/enzymology, Cell Transformation, Neoplastic, DNA Primers, DNA-Binding Proteins, Esophageal Neoplasms/enzymology, Gene Expression Regulation, Neoplastic, Humans, RNA, RNA, Messenger/analysis, Reverse Transcriptase Polymerase Chain Reaction, Telomerase/genetics
in
Journal of Gastrointestinal Surgery
volume
4
issue
2
pages
8 pages
publisher
Springer
external identifiers
  • pmid:10675236
  • scopus:0034146097
ISSN
1091-255X
DOI
10.1016/S1091-255X(00)80049-9
language
English
LU publication?
no
id
52baba83-e273-4aea-9cbb-d903448c6218
date added to LUP
2019-05-26 16:46:05
date last changed
2024-05-28 13:20:18
@article{52baba83-e273-4aea-9cbb-d903448c6218,
  abstract     = {{<p>Barrett's esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and esophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases. To identify biomarkers associated with each stage of the Barrett's process, relative mRNA expression levels of hTERT were measured using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector (TaqMan system) in Barrett's intestinal metaplasia (n = 14), Barrett's dysplasia (n = 10), Barrett's adenocarcinoma (n = 14), and matching normal squamous esophagus tissues (n = 32). hTERT expression was significantly increased at all stages of Barrett's esophagus, including the intestinal metaplasia stage, compared to normal tissues from patients without cancer (intestinal metaplasia vs. normal esophagus, P &lt;0.0001; dysplasia, P = 0.001; adenocarcinoma, P = 0.007; all Mann-Whitney U test ). hTERT expression levels were significantly higher in adenocarcinoma tissues than in intestinal metaplasia tissues (P = 0.003), and were higher in dysplasia compared with intestinal metaplasia tissues (P = 0.056). hTERT levels were also significantly higher in histologically normal squamous esophagus tissues from cancer patients than in normal esophagus tissues from patients with no cancer (P = 0.013). Very high expression levels ([hTERT x 100: beta-actin] &gt;20) were found only in patients with cancer. These findings suggest that telomerase activation is an important early event in the development of Barrett's esophagus and esophageal adenocarcinoma, that very high telomerase levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients with Barrett's cancer.</p>}},
  author       = {{Lord, R V and Salonga, D and Danenberg, K D and Peters, J H and DeMeester, T R and Johansson, J and Skinner, K A and Chandrasoma, P and DeMeester, S R and Bremner, C G and Tsai, P I and Danenberg, P V}},
  issn         = {{1091-255X}},
  keywords     = {{Adenocarcinoma/enzymology; Barrett Esophagus/enzymology; Cell Transformation, Neoplastic; DNA Primers; DNA-Binding Proteins; Esophageal Neoplasms/enzymology; Gene Expression Regulation, Neoplastic; Humans; RNA; RNA, Messenger/analysis; Reverse Transcriptase Polymerase Chain Reaction; Telomerase/genetics}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  pages        = {{42--135}},
  publisher    = {{Springer}},
  series       = {{Journal of Gastrointestinal Surgery}},
  title        = {{Telomerase reverse transcriptase expression is increased early in the Barrett's metaplasia, dysplasia, adenocarcinoma sequence}},
  url          = {{http://dx.doi.org/10.1016/S1091-255X(00)80049-9}},
  doi          = {{10.1016/S1091-255X(00)80049-9}},
  volume       = {{4}},
  year         = {{2000}},
}