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

Tamer Refaat, Eric D. Donnelly, Sean Sachdev, Vamsi Parimi, Samar El Achy, Prarthana Dalal, Mohamed Farouk, Natasha Berg, Irene Helenowski, Jeffrey P. Gross, John Lurain, Jonathan B. Strauss, Gayle Woloschak, Jian Jun Wei, William Small*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)590-597
Number of pages8
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume40
Issue number6
DOIs
StatePublished - Jan 1 2017

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Keywords

  • c-Met
  • cervical cancer
  • concurrent chemoradiation
  • overexpression
  • treatment outcomes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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