Background Synovial sarcomas account for up to 10 percent ofsoft-tissue sarcomas and include two major histologic subtypes,biphasic and monophasic, defined respectively by the presenceand absence of glandular epithelial differentiation in a backgroundof spindle tumor cells. A characteristic SYT–SSX fusiongene resulting from the chromosomal translocation t(X;18)(p11;q11)is detectable in almost all synovial sarcomas. The translocationfuses the SYT gene from chromosome 18 to either of two highlyhomologous genes at Xp11, SSX1 or SSX2.SYT–SSX1 and SYT–SSX2are thought to function as aberrant transcriptional regulators.We attempted to determine the influence of the two alternativeforms of the SYT–SSX fusion gene on tumor morphology andclinical outcome in patients with this sarcoma.
Methods We analyzed SYT–SSX fusion transcripts in 45 synovialsarcomas (33 monophasic and 12 biphasic) by the reverse-transcriptasepolymerase chain reaction and compared the results with relevantclinical and pathological data.
Results The SYT–SSX1 and SYT–SSX2 fusion transcriptswere detected in 29 (64 percent) and 16 (36 percent) of thetumors, respectively. There was a significant relation (P =0.003) between histologic subtype (monophasic vs. biphasic)and SSX1 or SSX2 involvement in the fusion transcript: all 12biphasic synovial sarcomas had an SYT–SSX1 fusion transcript,and all 16 tumors that were positive for SYT–SSX2 weremonophasic. Kaplan–Meier analysis of 39 patients withlocalized tumors showed that the 15 patients with SYT–SSX2had significantly better metastasis-free survival than the 24patients with SYT–SSX1 (P = 0.03 by multivariate analysis;relative risk, 3.0). There were no significant correlationsbetween the type of SYT–SSX transcript and age, sex, tumorlocation and size, whether there were metastases at diagnosis,or whether patients underwent chemotherapy. Histologic subtypealone was not prognostically important.
Conclusions The type of SYT–SSX fusion transcript correlateswith both the histologic subtype and the clinical behavior ofsynovial sarcoma. SYT–SSX fusion transcripts are a definingdiagnostic marker of synovial sarcomas and may also yield importantindependent prognostic information.
Source Information
From the Departments of Surgery (A.K., J.H.H., M.F.B.), Pathology (J.W., C.R.A., M.L.), and Human Genetics (M.L.), Memorial Sloan-Kettering Cancer Center, New York.
Address reprint requests to Dr. Ladanyi at the Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.
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