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Human Telomerase Reverse Transcriptase mRNA Expression Assessed by Real-Time Reverse Transcription Polymerase Chain Reaction Predicts Chemosensitivity in Patients With Ovarian Carcinoma

Fiamma Buttitta, Caterina Pellegrini, Antonio Marchetti, Angiolo Gadducci, Stefania Cosio, Lara Felicioni, Fabio Barassi, Simona Salvatore, Carla Martella, Guido Coggi, Silvano Bosari

From the Department of Oncology and Neurosciences, University of Chieti, Chieti; Department of Medicine, Surgery and Dental Sciences, Division of Pathology, University of Milan, Milan; A.O. S. Paolo, IRCCS Ospedale Maggiore and Interuniversity Center of Oncological Research, Milan; and Department of Procreative Medicine, Division of Gynecology and Obstetrics, University of Pisa, Italy.

Address reprint requests to Fiamma Buttitta MD, PhD, Molecular Pathology Section, Department of Oncology and Neurosciences, Anatomia Patologica, Ospedale Clinicizzato, via dei Vestini, 66013 Chieti, Italy; email: fbuttitta{at}unich.it.

Purpose: To evaluate in vivo whether the expression of the human telomerase reverse transcriptase (hTERT) gene, the catalytic subunit of the telomerase complex, is predictive of response to chemotherapy in ovarian cancer patients.

Patients and Methods: Fifty-nine advanced-stage ovarian cancer patients who were treated with platinum-based chemotherapy were studied. hTERT levels were evaluated by real-time reverse transcriptase polymerase chain reaction (RT-PCR) on tumor specimens obtained before the treatment. Variables were analyzed by the ² and Fisher’s exact tests. Logistic regression analysis was also performed to account for the effects of all the covariates investigated (residual disease, stage, histotype, and grade).

Results: Twenty-eight (47%) of the 59 tumors showed low hTERT levels, whereas 31 (53%) tumors displayed high hTERT levels. Seventy-five percent of complete responders showed high levels of hTERT expression, whereas 66% of partial responders or nonresponders exhibited low hTERT levels (P = .002). Only residual disease and hTERT expression were independent predictors of response (odds ratios, 13.455 and 7.586, respectively). The combination of these two parameters provides powerful predictive information: 18 of the 20 patients with residual disease more than 2 cm and low hTERT levels were partial responders or nonresponders, whereas 11 of the 12 patients with residual disease less than 2 cm and high hTERT levels showed a complete response (² = 21,416; P < .00001).

Conclusion: Our data indicate that hTERT expression, measured by real-time RT-PCR, is a possible independent marker of response to platinum-based therapy in advanced stage ovarian cancer patients. Prospective validation of this marker will be required to further define its predictive value.

Supported by Consiglio Nazionale delle Ricerche (CNR), Progetto Strategico "Oncologia" (BRIDGE) CNR-MIUR, Ministero dell’Università e della Ricerca Scientifica e Tecnologica (MURST 2000), and Associazione Italiana per la Ricerca su Cancro (AIRC).

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