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 bcl2 over-expression characterizes the SS gene profile in addition to the non-random translocations. Here we show that the over-expression of an additional potentially antiapoptotic gene, the c-KIT gene, is associated with this tumour. Interestingly, whereas bcl2 over-expression appears to be restricted to the spindle cell tumoral component, c-kit mainly involves the epithelial component of biphasic SS. Twenty-three primary and metastatic samples from 21 patients were analysed by immunophenotyping (23/23), immunoprecipitations and Western blotting (3/23), and RT-PCR (23/23). Ten cases were biphasic and 13 monophasic in sub-type. Twelve, 10 and 1 case carried the SYT-SSX1, 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), suggesting the occurrence of an autocrine loop. Immunophenotyping, confirmed by biochemical analyses, showed a modulation of c-Kit expression which was faint in the spindle and strong in the epithelial component, respectively. The study was complemented by c-Met/HGF receptor/ligand expression and c-Met protein 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 anti-apoptotic role from BCL2 to c-KIT gene during the transition from the uncommitted spindle to the differentiated epithelial cells.
Tamborini
E
E
Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, 20133, Italy.
Papini
D
D
Mezzelani
A
A
Riva
C
C
Azzarelli
A
A
Sozzi
G
G
Pierotti
M A
MA
Pilotti
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002648:Child; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D011233:Precipitin Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000235:genetics*
D017931:DNA Primers; D015514:Oncogene Proteins, Fusion; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C116512:SYT-SSX fusion protein; D019089:Stem Cell Factor; D017228:Hepatocyte Growth Factor; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met