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

• Published in: Anticancer research Vol. 34; no. 1; pp. 385 - 391
• Main Authors: Braicu, Elena Ioana, Gasimli, Khayal, Richter, Rolf, Nassir, Mani, Kümmel, Sherko, Blohmer, Jens-Uwe, Yalcinkaya, Isil, Chekerov, Radoslav, Ignat, Iulia, Ionescu, Andra, Mentze, Monika, Fotopoulou, Christina, Pop, Carmen, Lichtenegger, Werner, Sehouli, Jalid
• Format: Journal Article
• Language: English
• Published: Greece 01-01-2014
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - mortality; Adenocarcinoma - therapy; Adult; Aged; Biomarkers, Tumor - blood; Carcinoma, Squamous Cell - blood; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - therapy; Chemoradiotherapy, Adjuvant - mortality; Female; Follow-Up Studies; Humans; Matrix Metalloproteinase 2 - blood; Matrix Metalloproteinase 9 - blood; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - mortality; Neoplasm Staging; Prognosis; Prospective Studies; Survival Rate; Tissue Inhibitor of Metalloproteinase-2 - blood; Uterine Cervical Neoplasms - blood; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - therapy; Vascular Endothelial Growth Factor A - blood; TIMP2; radiochemotherapy response; MMP9; MMP2; Cervical cancer; VEGFA
• ISSN: 1791-7530

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.
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.
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).
Our results indicate a predictive value of VEGFA and TIMP2 in monitoring cervical cancer patients undergoing radiochemotherapy.