Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas.

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Brahmi, M. | Lesluyes, T. | Dufresne, A. | Toulmonde, M. | Italiano, A. | Mir, O. | Le Cesne, A. | Valentin, T. | Chevreau, C. | Bonvalot, S. | Penel, Nicolas | Coindre, J. M. | Le Guellec, S. | Le Loarer, F. | Karanian, M. | Blay, J. Y. | Chibon, F.

Edité par CCSD ; European Society for Medical Oncology -

International audience. BackgroundWhile the anti-PDGFRA antibody olaratumab failed to confirm an impact on survival in unselected advanced soft tissue sarcoma (STS) patients, the level of expression and the prognosis of platelet-derived growth factor (PDGF) receptors and ligands in STS remain unclear.Patients and methodsWe analyzed PDGF ligands and receptors' expression levels in a series of 255 patients with different histologies of STS [gastrointestinal stromal tumor (GIST), myxoid liposarcoma (MLPS), sarcoma with complex genomics, synovial sarcoma (SyS)] with Agilent single-color micro-arrays. We explored expression levels as prognostic values in univariate and multivariate analysis using R software (version 3.4.2).ResultsComplex patterns of correlation of expression between ligands and receptors were observed for each histotype. PDGFA levels were highest in SyS and lowest in MLPS (P < 4 × 10−9), PDGFB and C levels were lower in GIST (P < 2 × 10−15 and P < 3 × 10−9) while PDGFD expression was similar across histological subtypes. PDGF receptor (PDGFR) A expression was lowest in MLPS (P < 0.002), whereas PDGFRB and L expressions were lowest in GIST and SyS (P < 0.0004). Interestingly, high PDGFA expression levels were associated with higher risk of metastasis (P = 0.006), whereas PDGFD levels above average were associated with a reduced risk of metastasis (P = 0.01) in univariate and multivariate analysis.ConclusionsThe expression of PDGF ligands and receptors varies across sarcoma histological subtypes. PDGFA and D expression levels independently and inversely correlate with the risk of metastatic relapse.

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