Prognostic potential of the telomerase subunit human telomerase reverse transcriptase in tumor tissue and nontumorous mucosa from patients with colorectal carcinoma.
BACKGROUND
The stabilization of telomere lengths by telomerase activation is an important step in carcinogenesis and cell immortalization. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of this enzyme. The objective of this study was to evaluate the use of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for the quantification of hTERT in tumor and nontumorous tissue samples.


METHODS
Matched samples of tumor and adjacent nontumorous mucosa samples from 57 patients with completely resected colorectal carcinoma (International Union Against Cancer Stage I-IV) who underwent complete resection (R0) were quantified for hTERT mRNA expression using real-time RT-PCR. The expression levels were correlated with histopathologic findings and with survival. The median follow-up was 76 months.


RESULTS
hTERT mRNA was expressed in all tumor samples and in all samples of adjacent mucosa. In 12 patients (21%), there was higher hTERT expression in tumor samples compared with nontumorous samples. Compared with tumor samples, the expression of hTERT in samples of nontumorous mucosa decreased with age (P = 0.06). hTERT mRNA expression in both tumor tissue and adjacent mucosa was correlated significantly with the histologic grade of colorectal carcinoma (P < 0.04 and P < 0.05, respectively). Patients with hTERT expression in tumor tissue in relation to the adjacent mucosa of > 0.57 had a significantly poorer overall survival compared with patients with lower hTERT ratios (P < 0.02). In addition to the established prognostic factor lymphatic vessel invasion, the hTERT ratio proved to be of independent prognostic value (P < 0.05).


CONCLUSIONS
The prognostic potential of hTERT in patients with colorectal carcinoma and the correlation of hTERT with tumor grade underlines the role of hTERT as a molecular marker for biologic tumor staging.
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
Werner
Martin
M
Lassmann
Silke
S
Ulm
Kurt
K
Nekarda
Hjalmar
H
Siewert
Joerg-Ruediger
JR
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase