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Anticancer Res. 2014 Jan;34(1):385-91.

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.

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  • 1Department of Gynecology, Campus Virchow Clinic, Charité Medical University Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. elena.braicu@charite.de.

Abstract

AIM:

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.

PATIENTS AND 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).

CONCLUSION:

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

KEYWORDS:

Cervical cancer; MMP2; MMP9; TIMP2; VEGFA; radiochemotherapy response

PMID:
24403492
[PubMed - indexed for MEDLINE]
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