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

• Published in: Clinical cancer research 2004-02, Vol.10 (3), p.938-943
• Main Authors: TAMBORINI, Elena, BONADIMAN, Lorena, GRECO, Angela, GRONCHI, Alessandro, RIVA, Carla, BERTULLI, Rossella, CASALI, Paolo G, PIEROTTI, Marco A, PILOTTI, Silvana
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Blotting, Western; Cell Line, Transformed; Cell Line, Tumor; Humans; Immunohistochemistry; Ligands; Medical sciences; Pharmacology. Drug treatments; Phosphorylation; Precipitin Tests; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-kit - metabolism; Receptor Protein-Tyrosine Kinases - metabolism; Receptor, Platelet-Derived Growth Factor beta - biosynthesis; Recombinant Fusion Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA - metabolism; RNA, Messenger - metabolism; Sarcoma, Synovial - metabolism; Sarcoma, Synovial - pathology; Stem Cell Factor - biosynthesis; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0059

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 β (PDGFRβ), 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ where their activation is sustained by an autocrine loop.