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Journal of Clinical Oncology, Vol 22, No 10 (May 15), 2004: pp. 1807-1814
© 2004 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2004.09.160

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Telomere Length and Human Telomerase Reverse Transcriptase Expression As Markers for Progression and Prognosis of Colorectal Carcinoma

Ralf Gertler, Robert Rosenberg, Dominik Stricker, Jan Friederichs, Axel Hoos, Martin Werner, Kurt Ulm, Bernhard Holzmann, Hjalmar Nekarda, Joerg-Ruediger Siewert

From the Chirurgische Klinik und Poliklinik, Institut für Pathologie und Pathologische Anatomie, and Institut für Medizinische Statistik und Epidemiologie, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.

Address reprint requests to Ralf Gertler, MD, Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str 22, 81675 München, Germany; e-mail: gertler{at}nt1.chir.med.tu-muenchen.de

PURPOSE: Maintenance of telomeres through reactivation of telomerase is a prerequisite for tumors to preserve their ability to proliferate. The purpose of this study was to evaluate telomere length and human telomerase reverse transcriptase (hTERT) expression as markers for progression and prognosis of colorectal carcinoma.

PATIENTS AND METHODS: Telomere length and hTERT expression were analyzed in matched cancer and adjacent noncancer mucosa samples from 57 patients with R0-resected colorectal carcinoma. The median follow-up time was 76 months.

RESULTS: Telomere length and hTERT expression correlated significantly in cancer tissues and adjacent mucosa samples (r = 0.52, P < .001; and r = 0.54, P < .001, respectively). Overall, cancer tissue had shorter telomeres than adjacent mucosa (P < .001). Only in noncancer tissue did telomere length decrease with age (r = 0.36; P < .01). Telomere length in cancer tissue was significantly correlated with tumor stage (P < .01), with longer telomeres in advanced tumors. Patients with ratios of telomere length in cancer to noncancer tissue greater than 0.90 had a significantly poorer overall survival compared with patients with smaller telomere length ratios (P < .002). In multivariate analysis, the telomere length ratio proved to be of independent prognostic value (P < .03).

CONCLUSION: Telomeres in colorectal carcinoma tissue were significantly shorter compared with adjacent normal mucosa as an indication for extensive cell proliferation. The correlation with tumor stage and patient survival suggest that hTERT-mediated telomere stabilization may be critical for progression and prognosis of colorectal carcinoma.

Authors' disclosures of potential conflicts of interest are found at the end of this article.


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