Synovial sarcoma : a Scandinavian sarcoma group project

Sammanfattning: Synovial sarcoma accounts for 5 to 10 % of all soft tissue sarcomas. More than 90 % are found in the extremities or trunk wall. Characteristic for synovial sarcoma is the translocation t(X; 18) (p11.2;q11.2). Cloning of the breakpoints of this translocation revealed fusion of two novel genes, SYT and SSX. The SYT gene, located on chromosome 18, is fused with one of three closely related genes; SSX1, SSX2 or SSX4 located on the X chromosome. The long term survival rates have continuously improved and have at best been reported to around 50 %. However, since almost no population based studies on synovial sarcoma have been reported, these improvements may be due to differences in patient selection due to a changes in referral practice. This project was based on a consecutive series of synovial sarcoma patients from the Scandinavian Sarcoma Group Register acquired during a 9-year period. Only surgically treated patients without metastases at diagnosis were included in the prognostic analyses. The tumors were defined clinically, histopathologically, molecular and cytogenetically and these features were related to clinical course. 34 of 104 patients developed metastases. The overall 5 and 7 years survival rates were 0.76 (95% CI 0.66-0.83) and 0.69 (0.58-0.78), respectively. Large tumor size and amputation were significantly associated with impaired metastasis free survival. In addition, patients with local recurrence had a higher risk for metastases following the local event. Histologically, all were high grade lesions, 74 Grade III and 30 IV. Kaplan-Meier estimates of metastasis-free survival at 5 years were 83% (95% CI 72-92%) for patients with Grade III tumors versus 31% (95% CI 13-5 1%) for Grade IV. Histologic grading conveyed more prognostic information than any single histologic factor. Immunostaining with anti-Ki-67 antibodies (MIB1) and p53 based on formalin-fixed paraffinembedded material from 86 patients revealed that MIB1 > 10% was associated with poorer metastasis-free survival but p53 was not. Type of fusion transcripts (SYT-SSX1 or SYT-SSX2) and Ki-67 were assessed in fresh frozen tissue from 33 patients. The 5-year metastasis-free survival for patients with SYT-SSX1 was 42% versus 89% for those with SYT-SSX2. The hazard ratio for metastasis associated with the SYT-SSX1 fusion transcripts was 7 (95% CI 1.5-36, log-rank P=0.004). There was a significant association between SYT-SSX1 and high tumor proliferation rate. Comparative Genomic Hybridization revealed DNA sequence copy number changes in 35 of 69 tumor specimens. The frequency of aberrations/ tumor were higher in monophasic tumors than in biphasic. Gains of chromosome 8 were associated with large tumors (>5 cm). There was no obvious association between secondary aberrations and clinical outcome. In conclusion, large tumor size, local recurrence, histologic Grade IV, MIB1 index > 10 and possibly SYT-SSX1 fusion transcript were associated with impaired clinical outcome.