Basic fibroblast growth factor-2/beta3 integrin expression profile: signature of local progression after chemoradiotherapy for patients with locally advanced non-small-cell lung cancer.
OBJECTIVE
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 alphavbeta3 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
FGF-2, beta3 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 beta3 integrin (beta3(+)), 43% FGF-2 (FGF-2(+)), 41.5% syndecan-1, and 59.4% angiopoietin-2. Our results showed a strong association between FGF-2 and beta3 integrin expression (p = .001). The adjusted hazard ratio of local recurrence for FGF-2(+)/beta3(+) tumors compared with FGF-2(-)/beta3(-) 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 beta3 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.


CONCLUSIONS
The results of this study have identified the combined profile FGF-2/beta3 integrin expression as a signature of local control in patients treated with chemoradiotherapy for locally advanced NSCLC.
Massabeau
Carole
C
Département de Radiothérapie, Institut Claudius Regaud, 20-24 rue du Pont St. Pierre, Toulouse Cedex, France.
Rouquette
Isabelle
I
Lauwers-Cances
Valérie
V
Mazières
Julien
J
Bachaud
Jean-Marc
JM
Armand
Jean-Pierre
JP
Delisle
Marie-Bernadette
MB
Favre
Gilles
G
Toulas
Christine
C
Cohen-Jonathan-Moyal
Elizabeth
E
D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy / Q000379:methods; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D016016:Proportional Hazards Models; D011836:Radiation Tolerance; D053668:Syndecan-1 / Q000378:metabolism
D042702:Angiopoietin-2; D039661:Integrin beta3; D009363:Neoplasm Proteins; D053668:Syndecan-1; D016222:Fibroblast Growth Factor 2