SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma Journal Article
| Authors: | Kawai, A.; Woodruff, J.; Healey, J. H.; Brennan, M. F.; Antonescu, C. R.; Ladanyi, M. |
| Article Title: | SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma |
| Abstract: | 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 function 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 an 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. |
| Keywords: | adolescent; adult; cancer survival; clinical article; controlled study; aged; middle aged; survival analysis; proto-oncogene proteins; proteins; metastasis; reverse transcription polymerase chain reaction; neoplasm proteins; histology; transcription factors; gene fusion; oncogene proteins, fusion; chromosome translocation; x chromosome; translocation, genetic; synovial sarcoma; sarcoma, synovial; repressor proteins; chromosome 18; chromosome 11q; chromosome xp; chromosome 11p; chromosomes, human, pair 18; humans; prognosis; human; male; female; priority journal; article |
| Journal Title: | New England Journal of Medicine |
| Volume: | 338 |
| Issue: | 3 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 1998-01-15 |
| Start Page: | 153 |
| End Page: | 160 |
| Language: | English |
| DOI: | 10.1056/nejm199801153380303 |
| PUBMED: | 9428816 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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