The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome.
Cytogenetically, synovial sarcoma (SS) is characterized by the translocation t(X;18)(p11.2;q11.2), resulting in a fusion between the SYT gene on chromosome 18 and SSX1 or SSX2 on the X chromosome and the formation of new chimeric genes, SYT-SSX1 or SYT-SSX2. We examined the potential clinical relevance of SYT-SSX1 and SYT-SSX2 fusion transcripts together with tumor proliferation. In a series of 33 patients with primary SS, the type of fusion transcript was assessed by reverse transcription-PCR and sequence analysis. The proliferation rate was analyzed using anti-Ki-67 antibodies. One case carrying an atypical transcript with a 57-bp insert was excluded, leaving 13 SYT-SSX1 and 19 SYT-SSX2 cases for analysis. The hazard ratio (with respect to metastasis-free survival for patients with SYT-SSX1 versus patients with SYT-SSX2 fusion transcripts was 7.4 (95% confidence interval, 1.5-36; log-rank P = 0.004). There was also an association with reduced overall survival for patients with SYT-SSX1 compared to patients with SYT-SSX2 (hazard ratio, 8.5; 95% confidence interval, 1.0-73; log-rank P = 0.02). The 5-year metastasis-free survival for patients with SYT-SSX1 was 42% versus 89% for patients with SYT-SSX2. There was a significant association between SYT-SSX1 and a high tumor proliferation rate (P = 0.02). We conclude that the findings suggest that the type of SYT-SSX fusion transcript determines the proliferation rate and is an important predictor of clinical outcome in patients with SS.
Cellular and Molecular Tumor Pathology, CCK, Karolinska Hospital, Stockholm, Sweden.
G
G
Nilsson
B
B
Skytting
Y
Y
Xie
B
B
Brodin
R
R
Perfekt
N
N
Mandahl
J
J
Lundeberg
M
M
Uhlén
O
O
Larsson
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D002455:Cell Division; D002648:Child; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D018572:Disease-Free Survival; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011237:Predictive Value of Tests; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016415:Sequence Alignment; D015996:Survival Rate; D014178:Translocation, Genetic; D016896:Treatment Outcome; D014960:X Chromosome
D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein