title: c-Met Overexpression in Cervical Cancer, a Prognostic Factor and a Potential Molecular Therapeutic Target.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  c-Met overexpression could be a potential predictive marker and therapeutic target for local-regional advanced cervical cancer patients treated definitively with CRT.
authors.affiliation: Departments of Radiation Oncology.|Northwestern Medicine Developmental Therapeutics Institute (NMDTI).|Departments of Clinical Oncology and Nuclear Medicine.
authors.forename: Tamer
authors.initials: T
authors.lastname: Refaat
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Donnelly
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Sean
authors.initials: S
authors.lastname: Sachdev
authors.affiliation: Pathology.
authors.forename: Vamsi
authors.initials: V
authors.lastname: Parimi
authors.affiliation: Surgical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Samar
authors.initials: S
authors.lastname: El Achy
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Prarthana
authors.initials: P
authors.lastname: Dalal
authors.affiliation: Departments of Clinical Oncology and Nuclear Medicine.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Farouk
authors.affiliation: Pathology.
authors.forename: Natasha
authors.initials: N
authors.lastname: Berg
authors.affiliation: Preventive Medicine.
authors.forename: Irene
authors.initials: I
authors.lastname: Helenowski
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Gross
authors.affiliation: Obstetrics and Gynecology, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center.
authors.forename: John
authors.initials: J
authors.lastname: Lurain
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Strauss
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Gayle
authors.initials: G
authors.lastname: Woloschak
authors.affiliation: Pathology.|Obstetrics and Gynecology, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wei
authors.affiliation: Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University, Chicago, IL.
authors.forename: William
authors.initials: W
authors.lastname: Small
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015996:Survival Rate; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy
chemical_list: C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met