A case series of 64 synovial sarcomas was characterized for the SYT-SSX fusion transcripts and statistically analysed in order to correlate molecular data with prognosis and morphology. SYT-SSX1 fusion transcript appeared to be an independent, though not reaching statistical significance (P = 0.183), prognostic factor clearly associated with a reduced metastasis-free survival. Regarding the association between transcript type and histologic subtype we found, a borderline P value (P = 0.067) between the SYT-SSX1 transcript and the biphasic subtype which, subsequently expanding the analysis to 70 cases, turned out to be significant. However, we could not confirm the prediction value of the biphasic subtype for the presence of the SYT-SSX1 transcript since in our hands 6 out 33 (18%) biphasic tumours carried the SYT-SSX2 transcript.© 2001 Cancer Research Campaign http://www.bjcancer.com
SUMMARY:The translocation t(X;18) is currently regarded as a specific molecular marker of synovial sarcoma (SS). Recently, however, it has been reported that malignant peripheral nerve sheath tumors expressed this marker in 75% of the cases. To test independently this iconoclastic claim, a molecular analysis for the detection of the SYT-SSX fusion genes was carried out using archival material of 34 consecutive cases diagnosed as malignant peripheral nerve sheath tumors and treated in our Institute from 1998 to 2000. In four of these cases, the molecular analysis on fixed tissues was supplemented with an analysis on fresh frozen tissue. RNA extracted from formalin-fixed paraffin-embedded tissue blocks was evaluated for the presence of SYT-SSX1 and SYT-SSX2 fusion transcripts by RT-PCR. This analysis was extended to a wide variety of normal tissues simultaneously extracted and equally processed. Only two of the cases studied harbored SYT-SSX1 and SYT-SSX2 fusion transcripts, respectively. The diagnostic reevaluation of these two cases in light of the molecular data disclosed that one had the features of a monophasic SS and the other was compatible with that entity. Both of these tumors were strongly immunoreactive for bcl-2, confirming the diagnostic utility of this marker in this instance. Our results reaffirm the specificity of SYT-SSX for SS and suggest that an opposite claim made in a recent study may have been due to a faulty interpretation of the molecular results caused by a contamination of the samples. (Lab Invest 2002, 82:609 -618).
Summary Synovial sarcoma (SS) is cytogenetically characterized by the translocation t(X;18)(p11.2-q11.2) generating a fusion between the SYT gene on chromosome 18 and one member of the SSX family gene (SSX1; SSX2; SSX4) on chromosome X. Here, we report for the first time that 2 forms of SYT mRNA are present in both normal tissues and SSs. By amplifying the full-length SYT cDNA of two SSs, we detected 2 bands, here designated N-SYT and I-SYT. The latter, previously undescribed, contains an in-frame insertion of 93 bp. Its sequencing revealed a 100% homology with the mouse SYT gene. These two SYT forms were present, although in different amounts, in all human normal tissues examined, including kidney, stomach, lung, colon, liver and synovia. Coexistence of N-SYT and I-SYT (both fused with SSX) was detected in a series of 59 SSs (35 monophasic and 24 biphasic) and in a SS cell line. A preliminary analysis of the differential expression levels of N-SYT and I-SYT in SSs revealed that the latter was consistently overexpressed, suggesting a role in SS pathogenesis. 1087-1094 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2001.1710, available online at http://www.idealibrary.com on http://www.bjcancer.com MATERIALS AND METHODS Tumours and patients59 SSs were analysed by RT-PCR on frozen material. 31 showed the non-random translocation SYT-SSX1, 16 the SYT-SSX2 and one the SYT-SSX4; in the remaining 11 tumours no specific fusion transcript has been yet detected and these are the subject of further studies. Among the SYT-SSX1 tumours, 16/31 (51.6%) were monophasic and 15/31 (48.4%) biphasic; in the SYT-SSX2 group 12/16 (75%) were monophasic and 4/16 (25%) biphasic. The single SYT-SSX4 tumour was monophasic. There were 21 primary tumours, 15 local relapses and 23 metastases; in 2 cases (patients n. 27 and 42) we analysed both the primary tumour and the metastasis, and in 4 cases (patients n. 25, 28, 41 and 55) we analysed relapses and/or metastases ( Table 2).The human synovial sarcoma CME cell line was kindly provided by Dr B Kazmierczak (Renwick et al, 1995); these cells had the typical (X;18) translocation and showed the SYT-SSX2 fusion transcript.6 normal tissue samples (kidney, stomach, liver, lung, colon and synovia) derived from different patients surgically treated in our Institute were also analysed. RNA extraction and reverse-transcription reaction (RT-PCR)Total RNA was extracted using the RNAzol method (GIBCO BRL, Life Technology) from snap-frozen tissue samples stored at -80˚C. One µg of RNA was reverse-transcribed to cDNA with oligo(dT) and random examers primers, using Superscript II reverse transcriptase (GIBCO BRL, Paisley, UK), according to the manufacturer's conditions. One µl of cDNA was used as template for each PCR reaction, which was performed using AmpliTaq (Perkin Elmer), according to the manufacturer's conditions. All the amplification products were stained with ethidium bromide and analysed on 1.8% agarose gel. SYT-SSX PCRThe detection of the putative SYT-SSX1 or SYT-SSX2 fusion transcript ...
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