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Catalytic Subunit of Human Telomerase Reverse Transcriptase Is an Independent Predictor of Survival in Patients Undergoing Curative Resection of Hepatic Colorectal Metastases: A Multicenter Analysis

From the Departments of Medicine, Biostatistics, and Surgery, Institut Gustave Roussy, Villejuif; Centre de Chirurgie Viscerale et de Transplantation, Hopital de Hautepierre, Strasbourg; Commisariat à l'Energie Atomique, Fontenay-aux-roses, France; and the Departments of Surgical Oncology, Gastrointestinal Medical Oncology, and Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX

Address reprint requests to Jean-Charles Soria, MD, PhD, Institut Gustave Roussy, Division of Cancer Médecine, 39 Rue Camille Desmoulins, 94805 Villejuif, France; e-mail: soria{at}igr.fr; or Jean-Nicolas Vauthey, MD, Department of Surgical Oncology, Unit 444, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: jvauthey{at}mdanderson.org

PURPOSE: To determine the role of the catalytic subunit of human telomerase reverse transcriptase (hTERT) in predicting survival after resection of hepatic colorectal metastases (CRM).

PATIENTS AND METHODS: Two hundred one patients who underwent curative resection of hepatic CRM between 1990 and 2000 were identified from a multicenter database. The CRM were analyzed for hTERT nucleolar expression by standard immunohistochemical techniques. hTERT expression and known clinicopathologic factors of survival were examined.

RESULTS: With a median follow-up of 80 months, 152 patients (75.6%) had died; the 5-year overall survival was 30.7%. On univariate analysis, number of metastases greater than two (P = .0005), extrahepatic disease (P = .0054), disease-free interval less than 12 months (P = .006), carcinoembryonic antigen level greater than 200 ng/mL (P = .0071), and positive hTERT nucleolar staining (P < .0001) were associated with decreased survival. On multivariate analysis, three factors independently predicted survival: number of metastases (relative risk [RR] = 1.74; P = .0011); disease-free interval (RR = 1.70; P = .0035); and positive hTERT nucleolar staining (RR = 2.03; P < .0001). Patients with none or one of these factors had a 5-year survival rate of 48%, whereas those with two or three of these factors had a 5-year survival of 15% (P < .0001).

CONCLUSION: hTERT nucleolar expression is associated with worse survival after resection of hepatic CRM. hTERT expression in conjunction with number of hepatic metastases and disease-free interval may permit more accurate prediction of survival after resection of hepatic CRM.

Supported by a fellowship grant from the Foundation Bettencourt (J.D.).

Jean-Charles Soria and Jean-Nicolas Vauthey contributed equally to this work. This work is original. The analysis reported here has not previously been published in full or in part.

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

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