SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma

N Engl J Med. 1998 Jan 15;338(3):153-60. doi: 10.1056/NEJM199801153380303.


Background: Synovial sarcomas account for up to 10 percent of soft-tissue sarcomas and include two major histologic subtypes, biphasic and monophasic, defined respectively by the presence and absence of glandular epithelial differentiation in a background of spindle tumor cells. A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas. The translocation fuses the SYT gene from chromosome 18 to either of two highly homologous genes at Xp11, SSX1 or SSX2. SYT-SSX1 and SYT-SSX2 are thought to tunction as aberrant transcriptional regulators. We attempted to determine the influence of the two alternative forms of the SYT-SSX fusion gene on tumor morphology and clinical outcome in patients with this sarcoma.

Methods: We analyzed SYT-SSX fusion transcripts in 45 synovial sarcomas (33 monophasic and 12 biphasic) by the reverse-transcriptase polymerase chain reaction and compared the results with relevant clinical and pathological data.

Results: The SYT-SSX1 and SYT-SSX2 fusion transcripts were detected in 29 (64 percent) and 16 (36 percent) of the tumors, 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 12 biphasic synovial sarcomas had a SYT-SSX1 fusion transcript, and all 16 tumors that were positive for SYT-SSX2 were monophasic. Kaplan-Meier analysis of 39 patients with localized tumors showed that the 15 patients with SYT-SSX2 had significantly better metastasis-free survival than the 24 patients with SYT-SSX1 (P=0.03 by multivariate analysis; relative risk, 3.0). There were no significant correlations between the type of SYT-SSX transcript and age, sex, tumor location and size, whether there were metastases at diagnosis, or whether patients underwent chemotherapy. Histologic subtype alone was not prognostically important.

Conclusions: The type of SYT-SSX fusion transcript correlates with both the histologic subtype and the clinical behavior of synovial sarcoma. SYT-SSX fusion transcripts are a defining diagnostic marker of synovial sarcomas and may also yield important independent prognostic information.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chromosomes, Human, Pair 18
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins*
  • Oncogene Proteins, Fusion / genetics*
  • Prognosis
  • Proteins / genetics*
  • Proto-Oncogene Proteins
  • Repressor Proteins / genetics*
  • Sarcoma, Synovial / genetics*
  • Sarcoma, Synovial / pathology
  • Survival Analysis
  • Transcription Factors / genetics
  • Translocation, Genetic*
  • X Chromosome


  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • SS18 protein, human
  • Transcription Factors
  • synovial sarcoma X breakpoint proteins