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
Received 4 August 2008; received in revised form 19 November 2008; accepted 21 November 2008. published online 21 April 2009.
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.
∗Département de Radiothérapie, Institut Claudius Regaud, Toulouse, France
¶Département d'Oncologie, Institut Claudius Regaud, Toulouse, France
‖INSERM U563, Institut Claudius Regaud, Toulouse, France
†Service d'Anatomie Pathologique et Histologie-Cytologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
‡Service d'Epidémiologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
§Service de Pneumologie, Centre Hospitalier Universitaire de Toulouse, Hôpital Larrey, Toulouse, France
Reprint requests to: Elizabeth Cohen-Jonathan-Moyal, M.D., Ph.D., Département de Radiothérapie, Institut Claudius Regaud, 20-24 rue du Pont St. Pierre, Toulouse 31052 Cedex France. Tel: (33) 56-142-4178; Fax: (33) 56-142-4643
Supported by the Groupe de Recherche de l'Institut Claudius Regaud and the Institut National de la Santé et de la Recherche Médicale.
Presented at the French Society of Radiation Oncology (SFRO), Paris, 2007.
ABSTRACT