Identification of biological factors predictive of response to imatinib mesylate in aggressive fibromatosis.
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/microl) and tumour size >120 mm correlated with shorter PFS in univariate and multivariate analyses.


CONCLUSIONS
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.
Dufresne
A
A
Department of Medical Oncology and Department of Pathological Anatomy, Hospital Edouard Herrriot, Lyon, France.
Bertucci
F
F
Penel
N
N
Le Cesne
A
A
Bui
B
B
Tubiana-Hulin
M
M
Ray-Coquard
I
I
Cupissol
D
D
Chevreau
C
C
Perol
D
D
Goncalves
A
A
Jimenez
M
M
Bringuier
P P
PP
Blay
J Y
JY
D000328:Adult; D000368:Aged; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D018222:Desmoid Tumors / Q000188:drug therapy* / Q000628:therapy; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D011743:Pyrimidines; D016896:Treatment Outcome; D055815:Young Adult
D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit