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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ten Heuvel
Suzan E
SE
Department of Surgical Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
Hoekstra
Harald J
HJ
Suurmeijer
Albert J H
AJ
D014408:Biomarkers, Tumor; D005557:Formaldehyde; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000191:economics / Q000379:methods*; D015514:Oncogene Proteins, Fusion; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000191:economics / Q000379:methods*; D013584:Sarcoma, Synovial / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D012680:Sensitivity and Specificity; D012983:Soft Tissue Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D016707:Tissue Fixation
D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein; D005557:Formaldehyde