Diagnostic Application of Tumor Type-Specific Fusion Genes to Surgical Pathology of Bone and Soft Tissue Tumors: Experience Based on 200 Consultation Cases
M Hisaoka, A Matsuyama, H Hashimoto. School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
Background: Molecular detection of tumor type-specific fusion genes is a powerful diagnostic tool of bone and soft tissue tumors, which often create diagnostic challenges in surgical pathology. To highlight its utility and limitation, we itemize the consultation cases in which the molecular genetic testing was applied to their pathologic diagnoses.
Design: Among more than 4000 consultation cases sent to us in 1999-2008, we selected 200 consecutive cases in which RT-PCR-based molecular detection of a variety of fusion genes was performed using formalin-fixed, paraffin-embedded tissues (FFPE). Clinicopathologic findings of each case were reviewed and assessed with their initially assumed and final diagnoses.
Results: In the consultation cases, synovial sarcoma (39%) and the Ewing family of tumors (23%) were the most frequently intended tumor types for the molecular genetic testing. In 196 cases with informative RNA extracted from FFPE, tumor type-specific fusion gene transcripts were detected in 95 cases including six (three synovial sarcomas, one desmoplastic small round cell tumor, one extraskeletal myxoid chondrosarcoma and one dermatofibrosarcoma protuberans) morphologically and 33 clinically (i.e. age and anatomical location) unusual tumors. Although 72 of the 101 cases without detectable fusion gene transcripts showed more or less unusual histologic features as the tumor types amenable to their specific PCR, the other 21 cases were morphologically typical or compatible with translocation-associated sarcomas such as Ewing tumor (48% of 21 cases) and synovial sarcoma (29%). With the application of a novel primer set to the PCR, a rare splicing variant of SYT-SSX1 was detected in one such synovial sarcoma case that was initially 'fusion-negative'. No histologic slides were available for reviewing in the remaining eight cases lacking detectable fusion transcripts.
Conclusions: Our data suggests that the RT-PCR-based detection of the tumor type-specific fusion genes using FFPE is a robust molecular technique for confirming the diagnoses of translocation-associated sarcomas particularly in cases with unusual clinicopathologic features. In 'fusion-negative' but morphologically consistent cases, some technical modifications may improve detection sensitivity. In addition, an extended molecular testing would expand the morphologic diversity of translocation-associated sarcomas.
Category: Bone & Soft Tissue
Monday, March 22, 2010 1:00 PM
Poster Session II # 2, Monday Afternoon