Diagnostic accuracy of FISH and RT-PCR in 50 routinely processed synovial sarcomas

Molecular detection of SYT-SSX fusion genes is the most reliable tool for diagnosing synovial sarcoma (SS). The objective of this study was to investigate the accuracy of reverse transcription-polymerase chain reaction (RT-PCR) and a commercially available fluorescence in situ hybridization (FISH) technique for formalin-fixed and paraffin-embedded tumor tissue.

Fifty tumors with typical SS histology and 12 histologic mimics of SS were included. RT-PCR for SYT-SSX1/SSX2 gene fusions and FISH analysis for SYT gene breaks were performed on these 62 formalin-fixed and paraffin-embedded tumors.

All 50 SS were positive by either RT-PCR or FISH. Forty-seven SS (94%) were true positive by RT-PCR and 41 SS (82%) were true positive by FISH. FISH and RT-PCR results were interpretable and concordant in 38 cases (76%). Two cases were not interpretable by RT-PCR and 6 cases were not interpretable by FISH. One SS was false-negative with RT-PCR and 3 SS were false-negative with FISH. RT-PCR and FISH had a sensitivity of 94% and 82%, a specificity and positive predictive value of 100% and 100% and a negative predictive value of 80% and 75%, respectively.

RT-PCR had a higher sensitivity than FISH. One of both methods was always positive, whereas both methods were concordant in 76% of cases. From an economic point of view, we advocate to use FISH as a method of first choice, because it allows microscopic control of a true positive result (unpaired fluorescent signals in a break apart assay). Using this approach, 80% of SS can be diagnosed by FISH only and 20% would need to be confirmed by RT-PCR.