c-KIT and c-KIT ligand (SCF) in synovial sarcoma (SS): an mRNA expression analysis in 23 cases

In a previous immunophenotypic molecular-based analysis it was shown that b cl2 over-expression characterizes the SS gene profile in addition to the no n-random translocations. Here we show that the over-expression of an additi onal potentially antiapoptotic gene, the c-KIT gene, is associated with thi s tumour. Interestingly, whereas bcl2 over-expression appears to be restric ted to the spindle cell tumoral component, c-kit mainly involves the epithe lial component of biphasic SS. Twenty-three primary and metastatic samples from 21 patients were analysed by immunophenotyping (23/23), immunoprecipit ations and Western blotting (3/23), and RT-PCR (23/23). Ten cases were biph asic and 13 monophasic in sub-type. Twelve, 10 and 1 case carried the SYT-S SX1, SYT-SSX2 and SYT-SSX4 fusion transcript, respectively. Co-presence of both c-Kit and SCF mRNA was observed in almost all cases (20/23), suggestin g the occurrence of an autocrine loop. Immunophenotyping, confirmed by bioc hemical analyses, showed a modulation of c-Kit expression which was faint i n the spindle and strong in the epithelial component, respectively. The stu dy was complemented by c-Met/HGF receptor/ligand expression and c-Met prote in analysis with results superimposable to those already reported. Since in each tumour, epithelial and spindle cell components harbour the same type of translocation t(X;18) the present findings suggest a shifting of the ant i-apoptotic role from BCL2 to c-KIT gene during the transition from the unc ommitted spindle to the differentiated epithelial cells. (C) 2001 Cancer Re search Campaign.