Increased human telomerase reverse transcriptase (hTERT) mRNA expression but not telomerase activity is related to survival in curatively resected non-small cell lung cancer.
BACKGROUND
The purpose of this study was to evaluate the significance of human telomerase reverse transcriptase (hTERT) mRNA expression and telomerase activity as prognostic markers in non-small cell lung cancer (NSCLC).


METHODS
In a series of 69 curatively resected NSCLC specimens, telomerase activity was analyzed with the telomeric repeat amplification protocol (TRAP) assay and expression of hTERT mRNA by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Partitioning of gene expression levels and protein activities to construct prognostic groups was attempted.


RESULTS
Human hTERT mRNA transcripts were detected in 62 (89.9%) cases of NSCLC. Seven (10.1%) tumors were completely negative for hTERT expression. Dichotomized hTERT levels (<0.42 versus > or =0.42) were associated with prognosis and Kaplan-Meier survival curves demonstrated a significant difference (log rank: p<0.01) with 5-year survival rates of 44.3% (+/-7.1%) for low as compared to 80% (+/-8.9%) for high hTERT mRNA expression. Low hTERT expression was also significantly associated with squamous cell histology (p<0.03). Telomerase activity was not associated with survival, stage, pT and pN categories, histological type or grading. Comparison of hTERT mRNA expression and telomerase activity was possible in 66 patients and showed a significant difference (p<0.0001) by Wilcoxon rank test.


CONCLUSIONS
This is the first study which demonstrates that high hTERT mRNA expression is associated with improved 5-year survival rates. Expression patterns are distinct among histopathological subtypes of NSCLC and telomerase activity (TRAP) is significantly higher than hTERT mRNA expression.
Metzger
Ralf
R
Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Joseph-Stelzmann-Strasse 9, D-50931 Cologne, Germany. Ralf.Metzger@uk-koeln.de
Vallbohmer
Daniel
D
Müller-Tidow
Carsten
C
Higashi
Hiroshi
H
Bollschweiler
Elfriede
E
Warnecke-Eberz
Ute
U
Brabender
Jan
J
Baldus
Stephan E
SE
Xi
Huan
H
Berdel
Wolfgang E
WE
Serve
Hubert
H
Hoelscher
Arnulf H
AH
Schneider
Paul M
PM
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase