Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma

The hepatocyte growth factor (HGF)/c-MET signaling system plays an importan t role in the carcinogenesis of various organs. We investigated the express ion of HGF and its receptor c-MET by immunohistochemistry (IHC) in 69 cases of synovial sarcoma and compared the findings with clinicopathologic param eters, proliferating activities evaluated by MIB-1 labeling index (MIB-1 LI ), and patients' prognosis. Furthermore, mRNA analysis of HGF, c-MET, and S YT-SSX fusion gene was performed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 22 concordant frozen materials. Twenty-one of 69 (30.4 %) tumors showed positive reaction for c-MET,whereas 22 tumors (31.9%) were positive for HGF. In 10 cases, co-expression of HGF and c-MET was observed ; however, there was no significant correlation between HGF and c-MET expre ssion. HGF expression was correlated with female patients, large tumors (mo re than 5 cm), the presence of rhabdoid cells, low frequency of mast cells (<20/10 HPF), high nuclear grade (grade Iii), and high American Joint Commi ttee (AJC) stage (III and IV). Conversely, c-MET expression was only correl ated with large tumors. However, the coexpression of HGF and c-MET was sign ificantly correlated with large tumor size, the existence of rhabdoid cells , and high AJC stage. Both the expression of HGF and the co-expression of H GF and c-MET showed a significantly high MIB-1 LI and were correlated with poor prognosis according to univariate analysis. Multivariate Cox analysis showed that high AJC stage, the expression of HGF, and a high MIB-1 LI (12. 0>) independently had a negative impact on overall survival. In 22 frozen m aterial cases evaluated by both IHC and RT-PCR, a statistically significant correlation was found between the 2 techniques. SYT-SSX fusion transcripts were detected in all 22 cases. Three tumors had SYT-SSX2 fusion transcript s, whereas 19 had SYT-SSX1 phenotype. Our results suggest that HGF/c-MET pa racrine signaling may contribute to tumorigenesis and progression in synovi al sarcoma. Copyright (C) 2000 by W.B. Saunders Company.