Human Telomerase Reverse Transcriptase mRNA Expression Assessed by Real-Time Reverse Transcription Polymerase Chain Reaction Predicts Chemosensitivity in Patients With Ovarian Carcinoma
- 1 April 2003
- journal article
- gynecologic cancer
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 21 (7) , 1320-1325
- https://doi.org/10.1200/jco.2003.09.065
Abstract
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 χ2 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 (χ2 = 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.Keywords
This publication has 35 references indexed in Scilit:
- Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assaysJournal of Molecular Endocrinology, 2000
- FIGO staging classifications and clinical practice gudelines in the management of gynecologic cancersInternational Journal of Gynecology & Obstetrics, 2000
- Toward the Development of a Universal Grading System for Ovarian Epithelial CarcinomaGynecologic Oncology, 1998
- Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomasNature Genetics, 1998
- Telomerase Activity and Survival of Patients With Node-Positive Breast CancerJNCI Journal of the National Cancer Institute, 1997
- Telomerase Catalytic Subunit Homologs from Fission Yeast and HumanScience, 1997
- A novel method for real time quantitative RT-PCR.Genome Research, 1996
- Real time quantitative PCR.Genome Research, 1996
- Serum Half-Life of CA 125 during Early Chemotherapy as an Independent Prognostic Variable for Patients with Advanced Epithelial Ovarian Cancer: Results of a Multicentric Italian StudyGynecologic Oncology, 1995
- Is Telomerase a Universal Cancer Target?JNCI Journal of the National Cancer Institute, 1995