TY - JOUR
T1 - Identification of biological factors predictive of response to imatinib mesylate in aggressive fibromatosis
AU - Dufresne, A.
AU - Bertucci, F.
AU - Penel, N.
AU - Le Cesne, A.
AU - Bui, B.
AU - Tubiana-Hulin, M.
AU - Ray-Coquard, I.
AU - Cupissol, D.
AU - Chevreau, C.
AU - Perol, D.
AU - Goncalves, A.
AU - Jimenez, M.
AU - Bringuier, P. P.
AU - Blay, J. Y.
N1 - Funding Information:
Supported by grants from the INCa, the Comités du Rhône et de l’Ain de la Ligue contre le Cancer, and the Conticanet Network of Excellence (FP6-018806).
PY - 2010/8/10
Y1 - 2010/8/10
N2 - Background: Imatinib induces responses and disease stabilisations in non-resectable patients with aggressive fibromatosis (AF). The precise target of imatinib in AF and predictive factors for response to treatment are unknown. Methods: We investigated factors potentially predictive of response to imatinib in a series of 40 patients with progressive AF included in a phase II trial of imatinib: we tested the presence of KIT exon 10 variant (M541L), the expression of imatinib-sensitive kinases and cell cycle proteins by immunohistochemistry (IHC), and other clinical and biological factors. Results: Of 10 patients for whom DNA could be extracted, 3 had a KIT exon 10 variant (30%), with no correlation with response or progression-free survival (PFS). The expression of other imatinib targets (PDGFRA/B, macrophage colony-stimulating factor receptor (M-CSFR)) and of downstream components of the cell cycle, cell proliferation and proliferation pathway (cyclin D1, ERK, MEK 1-2) did not correlate with PFS. Pre-treatment lymphopenia (1500/l) and tumour size 120 mm correlated with shorter PFS in univariate and multivariate analyses.Conclusion:Our findings show that a baseline biological characteristic of the patient is the major parameter influencing response to imatinib in aggressive fibromatosis. Tumour characteristics, including the presence of a KIT exon 10 M541L variant, may influence tumour control but this needs to be confirmed and better explained.
AB - Background: Imatinib induces responses and disease stabilisations in non-resectable patients with aggressive fibromatosis (AF). The precise target of imatinib in AF and predictive factors for response to treatment are unknown. Methods: We investigated factors potentially predictive of response to imatinib in a series of 40 patients with progressive AF included in a phase II trial of imatinib: we tested the presence of KIT exon 10 variant (M541L), the expression of imatinib-sensitive kinases and cell cycle proteins by immunohistochemistry (IHC), and other clinical and biological factors. Results: Of 10 patients for whom DNA could be extracted, 3 had a KIT exon 10 variant (30%), with no correlation with response or progression-free survival (PFS). The expression of other imatinib targets (PDGFRA/B, macrophage colony-stimulating factor receptor (M-CSFR)) and of downstream components of the cell cycle, cell proliferation and proliferation pathway (cyclin D1, ERK, MEK 1-2) did not correlate with PFS. Pre-treatment lymphopenia (1500/l) and tumour size 120 mm correlated with shorter PFS in univariate and multivariate analyses.Conclusion:Our findings show that a baseline biological characteristic of the patient is the major parameter influencing response to imatinib in aggressive fibromatosis. Tumour characteristics, including the presence of a KIT exon 10 M541L variant, may influence tumour control but this needs to be confirmed and better explained.
KW - aggressive fibromatosis
KW - imatinib mesylate
KW - predictive factors
UR - http://www.scopus.com/inward/record.url?scp=77955511742&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6605783
DO - 10.1038/sj.bjc.6605783
M3 - Article
C2 - 20664593
AN - SCOPUS:77955511742
SN - 0007-0920
VL - 103
SP - 482
EP - 485
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 4
ER -