Telomere length and telomerase subunits as diagnostic and prognostic biomarkers in Barrett carcinoma.
BACKGROUND
Maintenance of telomeres has been identified as an essential regulator of proliferative capacity and genomic integrity in malignant tumors. The authors evaluated telomere length and telomerase subunits, hTR and hTERT, as prognostic markers in patients with Barrett carcinoma.


METHODS
Telomere length was measured by Southern blot analysis and hTR expression and hTERT expression by real-time polymerase chain reaction in both cancer tissue and adjacent noncancerous Barrett mucosa in resection specimens from 46 patients with Barrett carcinoma (International Union Against Cancer [UICC] stages I-III). The median follow-up time of the surviving patients was 79 months.


RESULTS
Cancer tissue expressed more hTERT-mRNA than noncancerous mucosa (P < .05). Telomere lengths in cancer tissue and in noncancerous mucosa increased with higher pT category (P = .08 and P = .05, respectively). Twenty-one patients who died of tumor recurrence showed significantly longer telomeres in cancer tissue compared with 25 patients without tumor-related deaths (P < .05). Telomere length in both cancer tissue and in noncancerous mucosa and the telomere-length ratio cancer:noncancerous tissue were correlated with overall survival. In multivariate analysis, the telomere-length ratio proved to be an independent prognostic parameter (P < .02; relative risk of death 3.4; confidence interval, 1.3-8.9). Ten patients with telomere-length ratios >1.17 had a significantly poorer overall survival compared with 36 patients with telomere-length ratios <or=1.17 with 5-year survival rates of 0% and 60%, respectively (P < .02).


CONCLUSIONS
Telomere length and telomerase subunits were identified as diagnostic and prognostic biomarkers for Barrett carcinoma. Genetic alterations found in adjacent noncancerous mucosa suggested a "field effect" in Barrett carcinoma.
Gertler
Ralf
R
Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. gertler@chir.med.tu-muenchen.de
Doll
Dietrich
D
Maak
Matthias
M
Feith
Marcus
M
Rosenberg
Robert
R
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015139:Blotting, Southern; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012313:RNA / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase