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 important role in the carcinogenesis of various organs. We investigated the expression of HGF and its receptor c-MET by immunohistochemistry (IHC) in 69 cases of synovial sarcoma and compared the findings with clinicopathologic parameters, proliferating activities evaluated by MIB-1 labeling index (MIB-1 LI), and patients' prognosis. Furthermore, mRNA analysis of HGF, c-MET, and SYT-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 expression. HGF expression was correlated with female patients, large tumors (more 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 Committee (AJC) stage (III and IV). Conversely, c-MET expression was only correlated with large tumors. However, the coexpression of HGF and c-MET was significantly correlated with large tumor size, the existence of rhabdoid cells, and high AJC stage. Both the expression of HGF and the co-expression of HGF 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 material 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 transcripts, whereas 19 had SYT-SSX1 phenotype. Our results suggest that HGF/c-MET paracrine signaling may contribute to tumorigenesis and progression in synovial sarcoma.
Oda
Y
Y
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Sakamoto
A
A
Saito
T
T
Kinukawa
N
N
Iwamoto
Y
Y
Tsuneyoshi
M
M
D000328:Adult; D014408:Biomarkers, Tumor; D005260:Female; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics*
D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C116512:SYT-SSX fusion protein; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met