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c-Met Overexpression in Cervical Cancer, a Prognostic Factor and a Potential Molecular Therapeutic Target

Refaat, Tamer MD, PhD, MSCI*,†,‡; Donnelly, Eric D. MD*; Sachdev, Sean MD*; Parimi, Vamsi MD§; El Achy, Samar MD, PhD; Dalal, Prarthana BA*; Farouk, Mohamed MD, PhD; Berg, Natasha MD§; Helenowski, Irene PhD; Gross, Jeffrey P. MD*; Lurain, John MD#; Strauss, Jonathan B. MD*; Woloschak, Gayle PhD*; Wei, Jian-Jun MD§,#; Small, William Jr MD, FACRO, FACR, FASTRO**

American Journal of Clinical Oncology: December 2017 - Volume 40 - Issue 6 - p 590–597
doi: 10.1097/COC.0000000000000203
Original Articles: Gynecological

Purpose: This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), distant metastases (DM) control, and local-regional control (LC).

Patients and Methods: This Institutional Review Board–approved study included cervical cancer patients treated definitively and consecutively with CRT. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes, and incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H score). Treatment outcomes were reviewed and reported. Outcomes were stratified by c-Met overexpression and tumor characteristics. OS, PFS, LC, and DC rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained via Cox regression for both univariate and multivariate analyses.

Results: The 5-year OS, PFS, LC, and DC were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. Ten (35.7%) and 18 patients (64.3%) had c-Met H index >30 and<30, respectively. c-Met overexpression was significantly associated with worse 3- and 5-year OS (P=0.003), PFS (P=0.002), LC (P=0.01), and DC (P=0.0003). Patients with c-Met overexpression had a hazard ratio of 6.297, 5.782, 6.28, and 18.173 for the risks of death, disease progression, local recurrence, and DM, respectively.

Conclusion: c-Met overexpression could be a potential predictive marker and therapeutic target for local-regional advanced cervical cancer patients treated definitively with CRT.

Departments of *Radiation Oncology

§Pathology

Preventive Medicine

#Obstetrics and Gynecology, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center

Northwestern Medicine Developmental Therapeutics Institute (NMDTI)

**Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University, Chicago, IL

Departments of Clinical Oncology and Nuclear Medicine

Surgical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

The authors declare no conflicts of interest.

Reprints: William Small, Jr, MD, FACRO, FACR, FASTRO, Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University, 2160 S 1st Ave, Maguire Center, Rm 2932, Chicago, Maywood, IL 60153. E-mail: wmsmall@lumc.edu.

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