Gene expression as a predictor of radiotherapy or chemoradiotherapy response in head and neck squamous cell carcinoma patients: A molecular approach.

Abstract

5590 Background: There are not validated markers of radioresistance in patients with a head and neck squamous cell carcinoma (HNSCC). The objective of our study was to explore the relationship between response to radiotherapy and the expression at transcriptional level of a panel of genes related with the HNSCC carcinogenic process. Methods: The study group was 76 consecutive HNSCC patients treated with radiotherapy (n=51) or chemoradiotherapy (n=25) with curative intention, and a minimum follow-up of three years. Thirty-seven patients were T1-T2 tumors and 16 had an advanced tumor (T3-T4). Biopsy specimens were performed from the primary tumor before treatment and conveniently stored until processing. Expression of genes related with cell cycle (cyclin D1), apoptosis (Bcl-XL), angiogenesis (VEGF), inflammation (IL-8), and tissue invasiveness (MMP-2 and MMP-9) were examined using a RT-PCR method. The continuous value of the mRNA expression level was evaluated with a classification and regression tree (CRT) method, considering the local control of the disease achieved with radiotherapy as the dependent variable. Results: During the follow-up 26 patients (33.8%) had a local failure. The CRT method found a significant relationship between VEGF and MMP-9 expression and local control of the disease. According the expression level of VEGF and MMP-9 the patients were classified in three groups: the A group (n=19) defined by a low expression of VEGF, the B group (n=19) defined by a high expression of VEGF and a low expression of MMP-9 and the C group (n=38) defined by a high expression of both VEGF and MMP-9. The 5-year local recurrence free survival was: A group 94.7% (CI 95%: 84.7-100%), B group 83.3% (CI 95%: 66.1-100%), and C group 37.6% (CI 95%: 21.0-54.2%). There were significant differences in the local control of the disease according to the VEGF and MMP-9 expression values (test log rank, P<0.0001). Conclusions: Expression of VEGF and MMP-9 genes may be a radiosensitivity marker for patients with HNSCC treated with radical intention. We didn’t find prognostic significance for other genes explored.