Synovial Sarcoma by Reverse Transcriptase PCR (RT-PCR), Paraffin
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Synovial sarcomas account for 9% to 10% of soft tissue tumors. These tumors occur in 2 major forms: biphasic and monophasic. Monophasic tumors are composed entirely of spindle cells, while biphasic tumors have epithelial cells arranged in glandular structures and mixed with spindle cells. The tumors are usually positive for keratin and epithelial membrane antigen as well as vimentin by immunostaining.
Synovial sarcoma is a member the small-round-cell tumor group that includes rhabdomyosarcoma, lymphoma, Wilms tumor, Ewing sarcoma, and desmoplastic small-round-cell tumor. While treatment and prognosis depend on establishing the correct diagnosis, the diagnosis of sarcomas that form the small-round-cell tumor group can be very difficult by light microscopic examination alone, especially true when only small needle biopsy specimens are available for examination. The use of immunohistochemical stains (eg, keratin and EMA) can assist in establishing the correct diagnosis, but these markers are not entirely specific for synovial sarcoma. Expertise in soft tissue and bone pathology are often needed.
Studies have shown that some sarcomas have specific recurrent chromosomal translocations. These translocations produce highly specific gene fusions that help define and characterize subtypes of sarcomas and are useful in the diagnosis of these lesions.(1-4)
Cytogenetic studies have shown a distinctive chromosomal translocation, t(X;18)(p11;q11), in more than 90% of synovial sarcomas. Cloning of the translocation breakpoint showed that t(X;18) results in the fusion of 2 genes designated as SYT (at 18q11) and SSX (at Xp11). Two closely related genes, SSX1 and SSX2, have 81% homology in proteins. SYT-SSX2 is present in 35% of cases. Patients with SYT-SSX2 translocation usually have greater metastasis-free survival than those with SYT-SSX1.
These fusion transcripts can be detected by reverse transcriptase PCR (RT-PCR), by FISH, chromogenic in situ hybridization (CISH), or by classical cytogenetic analyses. The RT-PCR and FISH procedures are the most sensitive methods to detect these fusion transcripts.(3)
Supporting a diagnosis of synovial sarcoma
A positive result is consistent with a diagnosis of synovial sarcoma.
Sarcomas other than synovial sarcoma, and carcinomas, melanomas, and lymphomas are negative for the fusion products.
A negative result does not rule out a diagnosis of synovial sarcoma.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Reliable results are dependent on adequate specimen collection, and processing. This test has been validated on formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause PCR failure.
Clinical diagnosis and/or therapy should not be based solely on the results of this assay. The results should be considered in conjunction with clinical information, histologic evaluation, and/or additional diagnostic tests.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Crew AJ, Clark J, Fisher C, et al: Fusion of SYT to two genes SSX1 and SSX2 encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J 1995;14:2333-2340
2. Clark J, Rocques PJ, Crew AJ, et al: Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nat Genet 1994;7:502-508
3. Kawaii A, Wodruff J, Healey JH, et al: SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med 1998;338:153-160
4. Jin L, Majerus J, Oliveira A, et al: Detection of fusion gene transcripts in fresh-frozen and formalin-fixed paraffin-embedded tissue sections of soft tissue sarcomas after laser capture microdissection and RT-PCR. Diagn Mol Pathol 2003;12:224-230