12. Molecular tools for diagnosis of synovial sarcomas: correlation of RT-PCR and fish on paraffin embedded material

Abstract

Background Synovial sarcomas (SS) comprise 8–10% of soft tissue tumours, may occur at any site, are histologically diverse, and immunohistochemistry is not diagnostic. This makes diagnosis difficult, particularly in SS arising in uncommon sites such as the thorax. SS are characterised by a (X;18) (p11.2;q11.2) chromosome translocation fusing SYT with any of several SSX genes to create a functional SYT-SSX fusion protein. Fluorescence in situ hybridisation (FISH) can detect the translocation on paraffin sections, but has limitations. Reverse transcription PCR may be more sensitive and provides DNA sequence information, but fresh material is rarely available. Aims To perform RT-PCR on archival paraffin-embedded blocks of SS in typical sites with typical morphology (low diagnostic ambiguity, n = 14;7) and in difficult SS cases (previously diagnosed as such based on traditional techniques) arising in the thorax (n = 14; 9). Methods RNA was extracted, reverse transcribed, the SYT-SSX translocation was amplified by PCR and se-quenced. Sections of the same block underwent FISH analysis. Results Of the typical SS cases, 6/7 (85.7%) amplified SYT-SSX, and 5/6 (83.3%) were concordant with FISH. Of the thoracic cases, 4/9 (44.4%) were SYT-SSX positive by PCR, concordant with FISH in 7/8 cases (87.5%). Conclusion RT-PCR correlates well (85% concordance) with FISH, but has greater sensitivity. In the atypical cases, less than 50% were confirmed as SS cases by molecular techniques, and the negative cases are now undergoing review. Molecular testing should be added to the repertoire of tools available for SS diagnosis, particularly when the cases are atypical or entirely monophasic. Acknowledgements L. M. Stimmler received an RCPA undergraduatescholarship (2007).