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Expression of Ligand-Activated KIT and Platelet-Derived Growth Factor Receptor ß Tyrosine Kinase Receptors in Synovial Sarcoma

¹ Experimental Molecular Pathology, Department of Pathology and Departments of ² Experimental Oncology, ³ Soft Tissue Surgery, and ⁴ Radiotherapy, Istituto Nazionale per lo Studio e al Cura dei Tumori, Milan, Italy, and ⁵ Istituto Federazione Italiana Ricerca Cancro Institute of Molecular Oncology, Milan, Italy

Purpose: The use of tyrosine kinase receptor inhibitors is increasingly becoming a valuable therapeutic alternative in tumors carrying activated tyrosine kinase receptors. In a previous study, we described a coexpression of KIT and stem cell factor (SCF) mRNA in Synovial sarcomas, (SS) and in a limited number of cases, we demonstrated the presence of an activated receptor. Here, in a wider number of cases, we investigated the expression level and phosphorylation status of two structurally related tyrosine kinase receptors, KIT and platelet-derived growth factor receptor ß (PDGFRß), at the light of their role as possible targets of tyrosine kinase receptors inhibitor molecules.

Experimental Design: Forty-three SS cases were analyzed for KIT and PDGFRß expression/activation by immunoprecipitation/Western blotting experiments. The cognate ligands, SCF and PDGFB, were detected by reverse transcription-PCR.

Results: KIT was observed in 48 and 41% (45% total) whereas PDGFRß in 54 and 33% (45% total) of monophasic and biphasic SS cases, respectively. With respect to the fusion transcript type SYTSSX1 and SYTSSX2, KIT was more expressed in SYTSSX1 carrying cases (48 versus 38%), whereas PDGFRß resulted more frequently expressed in SYTSSX2 ones (54 versus 37%). When expressed, the receptors were phosphorylated. Their ligands were detected in all of the activated cases.

Conclusions: About 70% of the cases express one of the two activated tyrosine kinase receptors with a mutually exclusive expression trend. Coexpression is not frequent and seems to be restricted to monophasic subtype. These data indicate that a consistent fraction of this tumor type could represent a good candidate for kinase inhibitor molecules effective on KIT and PDGFRß where their activation is sustained by an autocrine loop.

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