Basic Fibroblast Growth Factor-2/β3 Integrin Expression Profile: Signature of Local Progression After Chemoradiotherapy for Patients With Locally Advanced Non–Small-Cell Lung Cancer

Purpose

No biologic signature of chemoradiotherapy sensitivity has been reported for patients with locally advanced non–small-cell lung cancer (NSCLC). We have previously demonstrated that basic fibroblast growth factor (FGF-2) and αvβ3 integrin pathways control tumor radioresistance. We investigated whether the expression of the proteins involved in these pathways might be associated with the response to treatment and, therefore, the clinical outcome.

Methods and Materials

FGF-2, β3 integrin, angiopoietin-2, and syndecan-1 expression was studied using immunohistochemistry performed on biopsies obtained, before any treatment, from 65 patients exclusively treated with chemoradiotherapy for locally advanced NSCLC. The response to treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria using computed tomography at least 6 weeks after the end of the chemoradiotherapy. Local progression-free survival, metastasis-free survival, and disease-free survival were studied using the log–rank test and Cox proportional hazard analysis.

Results

Among this NSCLC biopsy population, 43.7% overexpressed β3 integrin (β3⁺), 43% FGF-2 (FGF-2⁺), 41.5% syndecan-1, and 59.4% angiopoietin-2. Our results showed a strong association between FGF-2 and β3 integrin expression (p = .001). The adjusted hazard ratio of local recurrence for FGF-2⁺/β3⁺ tumors compared with FGF-2⁻/β3⁻ tumors was 6.1 (95% confidence interval, 2.6–14.6, p = .005). However, the risk of local recurrence was not increased when tumors overexpressed β3 integrin or FGF-2 alone. Moreover, the co-expression of these two proteins was marginally associated with the response to chemoradiotherapy and metastasis-free survival.

Conclusion

The results of this study have identified the combined profile FGF-2/β3 integrin expression as a signature of local control in patients treated with chemoradiotherapy for locally advanced NSCLC.

Integrins, Basic fibroblast growth factor, FGF-2, Radiotherapy, Chemotherapy, Lung cancer