Diagnostic Utility of SS18-SSX Fusion-Specific and SSX C-Terminus Antibodies in Synovial Sarcoma: Validation in a Large Indian Tertiary Care Cohort

Diagnosis of synovial sarcoma (SS) requires molecular confirmation of the SS18-SSX fusion by FISH or RT-PCR, but these methods are costly and limited in resource-constrained settings. Recently developed fusion-specific antibodies offer potential alternatives, but validation in resource-limited settings remains limited. We evaluated SS18-SSX fusion-specific (E9X9V) and SSX C-terminus (E5A2C) antibodies in 50 FISH-confirmed SS cases and 50 histologic mimics from a tertiary cancer center (July 2023 to June 2025). Nuclear staining was scored (0 to 8 scale, grade 0 to 3; grade ≥2 considered positive). Five SS cases had technically noninterpretable SS18-SSX staining and were excluded from the analysis. Sensitivity, specificity, and predictive values were calculated with 95% CIs. SS18-SSX showed 95.6% sensitivity (43/45 interpretable SS cases; 95% CI: 84.9-99.5%) and 100% specificity (50/50 controls). SSX C-terminus demonstrated 100% sensitivity (50/50 SS) but 94.0% specificity (47/50 controls), with false positivity in 3 mimics (medullary thymoma, spindle cell rhabdomyosarcoma, and MPNST). SSX C-terminus showed perfect sensitivity, such that a negative stain effectively excludes synovial sarcoma, whereas SS18-SSX showed perfect specificity, such that a positive stain confirms the diagnosis. Sequential interpretation of both antibodies is a reliable, lower-cost alternative to molecular testing in resource-limited settings, with FISH reserved for indeterminate results.