043 - α3 integrin/FGF-2 expression profile: signature of local progression after chemo- radiotherapy for patients with NSCLC - 05/12/08
C. Massabeau [1],
I. Rouquette [2],
V. Cances-Lauwers [3],
C. Toulas [4],
J.-M. Bachaud5 [5],
E. Moyal [1 et 4],
J. Mazieres [4 et 5]
Voir les affiliationsPurpose: No biological signature of chemo-radiotherapy 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 vβ3 integrin pathways control tumor radioresistance. We now investigate whether the expression of the proteins involved in these pathways may be associated with the response to treatment and, therefore, the clinical outcome.
Methods: FGF-2, 3 integrin, angiopoietin-2 and syndecan-1 expressions were studied using immunohistochemistry performed on biopsies obtained, before any treatment, from 65 patients exclusively treated with chemo-radiotherapy for locally advanced NSCLC. Response to treatments was evaluated according to the RECIST criteria by CT-scan at least 6 weeks after the end of the chemo-radiotherapy. Local progression, metastasis and disease-free survivals were studied using log rank test and Cox proportional hazard analysis.
Results: Among this NSCLC biopsy population, 43.7% over- expressed 3 integrin ( 3+), 43% FGF-2 (FGF-2+), 41.5% syndecan-1 and 59.4% angiopoietin-2. Our results show a strong association between FGF-2 and 3 integrin expression (P=0,001). The adjusted hazard ratio of local recurrence of 3 +/ FGF-2+ tumors compared to FGF-2-/ 3- tumors was 6.1 (95% confidential interval = 2.6 to 14.6, P=0,005) whereas the risk of local recurrence was not increased when tumors overexpressed 3 or FGF-2 alone. Moreover, the co-expression of these two proteins is marginally associated with the response to chemo-radiotherapy and to metastasis free survival.
Conclusion: This study identifies the combined profile FGF-2/ 3 integrin expression as a signature of the local control in patients treated with chemo-radiotherapy for locally-advanced NSCLC.
© 2008 Elsevier Masson SAS. Tous droits réservés.