Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Gertler
Ralf
R
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. gertler@nt1.chir.med.tu-muenchen.de
Rosenberg
Robert
R
Stricker
Dominik
D
Friederichs
Jan
J
Hoos
Axel
A
Werner
Martin
M
Ulm
Kurt
K
Holzmann
Bernhard
B
Nekarda
Hjalmar
H
Siewert
Joerg-Ruediger
JR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015139:Blotting, Southern; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D016019:Survival Analysis; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D016615:Telomere / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase