title: Role of serum VEGFA, TIMP2, MMP2 and MMP9 in monitoring response to adjuvant radiochemotherapy in patients with primary cervical cancer--results of a companion protocol of the randomized NOGGO-AGO phase III clinical trial.
abstract: OBJECTIVE
  The aim of the current study was to analyze the type of variations in expression profiles of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase 2 (TIMP2), and vascular endothelial growth factor A (VEGFA) before and after radiochemotherapy in patients with locally advanced FIGO stage Ib-IIb cervical cancer. We analyzed the role of these biomarkers in monitoring response to treatment.
  
  
  METHODS
  Serum from 72 patients with cervical cancer treated within a phase III trial with either simultaneous radiochemotherapy (S-RC) with cisplatin, or systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R) was analyzed by ELISA. Sera were obtained during surgery and after the end of adjuvant treatment.
  
  
  RESULTS
  The median age at time of diagnosis was 46 years (range=30-71 years). The most common histological types were squamous cell (73.6%) and adenocarcinoma (25%). Thirty-five (48.6%) patients underwent surgery followed by S-RC and 37 (51.4%) patients were treated with surgery followed by PC-R. Five patients developed recurrence within six months after radiochemotherapy. VEGFA levels were significantly higher before and after adjuvant treatment in patients who developed early recurrence (p=0.001). An increase of more than 500 pg/ml VEGFA and a decrease of more than 9% of the pre-therapeutic value of TIMP2 were significantly associated with a higher risk of early recurrence (RR=8.5, 95% CI=1.8-39.8 and RR=11.0, 95% CI=2.5-48.2, respectively). TIMP2 expression and risk score for early relapse (which is calculated using values of VEGFA and TIMP2) were independent prognostic factors for overall survival (p=0.043, HR=0.96, 95% CI=0.93-0.99 and p=0.002, HR=1.09, 95% CI=1.03-1.15, respectively).
  
  
  CONCLUSIONS
  Our results indicate a predictive value of VEGFA and TIMP2 in monitoring cervical cancer patients undergoing radiochemotherapy.
authors.affiliation: Department of Gynecology, Campus Virchow Clinic, Charité Medical University Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. elena.braicu@charite.de.
authors.forename: Elena Ioana
authors.initials: EI
authors.lastname: Braicu
authors.forename: Khayal
authors.initials: K
authors.lastname: Gasimli
authors.forename: Rolf
authors.initials: R
authors.lastname: Richter
authors.forename: Mani
authors.initials: M
authors.lastname: Nassir
authors.forename: Sherko
authors.initials: S
authors.lastname: Kümmel
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Blohmer
authors.forename: Isil
authors.initials: I
authors.lastname: Yalcinkaya
authors.forename: Radoslav
authors.initials: R
authors.lastname: Chekerov
authors.forename: Iulia
authors.initials: I
authors.lastname: Ignat
authors.forename: Andra
authors.initials: A
authors.lastname: Ionescu
authors.forename: Monika
authors.initials: M
authors.lastname: Mentze
authors.forename: Christina
authors.initials: C
authors.lastname: Fotopoulou
authors.forename: Carmen
authors.initials: C
authors.lastname: Pop
authors.forename: Werner
authors.initials: W
authors.lastname: Lichtenegger
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality / Q000628:therapy; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000401:mortality / Q000628:therapy; D059186:Chemoradiotherapy, Adjuvant / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000401:mortality* / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C560823:TIMP2 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Cervical cancer; MMP2; MMP9; TIMP2; VEGFA; radiochemotherapy response