Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synovial sarcoma is a soft tissue malignancy defined by the SYT-SSX fusion oncogene. Demonstration of the t(X;18) by cytogenetics, fluorescence in situ hybridization or reverse-transcriptase polymerase chain reaction has become the gold standard for diagnosis, but practical considerations limit the availability of these methods. Gene expression profiling studies performed by several independent groups have consistently identified TLE1 as an excellent discriminator of synovial sarcoma from other sarcomas, including histologically similar tumors such as malignant peripheral nerve sheath tumor. TLE proteins (human homologues of Groucho) are transcriptional corepressors that inhibit Wnt signaling and other cell fate determination signals, and so have an established role in repressing differentiation. We examined the expression of TLE proteins in synovial sarcoma and in a broad range of mesenchymal tumors using tissue microarrays to assess the value of anti-TLE antibodies in the immunohistochemical confirmation of synovial sarcoma. We demonstrate that TLE expression is a consistent feature of synovial sarcoma using both a well-characterized monoclonal antibody recognizing the TLE family of proteins and a commercially available polyclonal antibody raised against TLE1. Both antibodies gave intense and/or diffuse nuclear staining in 91/94 molecularly confirmed synovial sarcomas. Moderate staining is occasionally seen in schwannoma and solitary fibrous tumor/hemangiopericytoma. In contrast, TLE staining is detected much less frequently and at lower levels, if at all, in 40 other mesenchymal tumors. Our findings establish TLE as a robust immunohistochemical marker for synovial sarcoma, and may have implications for understanding the biology of synovial sarcoma and for developing experimental therapies for this cancer.
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PMID:TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies. 1725 69

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is an extremely rare tumor of the thyroid and neck, first described by Chan and Rosai. SETTLE is a low-grade malignancy, with potential for late lung, lymph node, and other visceral metastases. The clinicopathologic features of SETTLE overlap significantly with those of synovial sarcoma. Thirteen cases previously diagnosed as "SETTLE" (11 cases) or "malignant neoplasm-SETTLE versus synovial sarcoma" (2 cases), were retrieved. Immunohistochemistry for low-molecular-weight cytokeratins, high-molecular-weight cytokeratins, cytokeratin 7, cytokeratin 20, epithelial membrane antigen, bcl-2, CD34, CD99, CD117, INI-1, and TLE1 were performed. Reverse transcriptase polymerase chain reaction for the SS18/SSX1 and SS18/SSX2 fusion genes and fluorescent in-situ hybridization for SYT rearrangement was performed. The 11 cases diagnosed, as "SETTLE" were negative for synovial sarcoma-associated fusion genes, whereas the other 2 cases were positive. SETTLE occurred in 7 females and 4 males (7 to 50 y of age, median 13.5 y) and involved the thyroid gland in 10 cases. Clinical follow-up showed 3 patients to be disease-free 7, 10, and 15 years after surgery. One patient had a lymph node metastasis at diagnosis and lung metastases 14 months after diagnosis. SETTLE infiltrated the thyroid, and consisted of a vaguely nodular admixture of fascicular, reticular, hyalinized, and microcystic areas. Spindled zones blended imperceptibly into areas showing epithelial differentiation, in the form of glomeruloid glandular structures, sertoli-like tubules, and small glands, lined by cuboidal to columnar cells. Mitotic activity was very low, necrosis was absent, and pleomorphism was not present. By immunohistochemistry, SETTLE showed extensive expression of high-molecular-weight cytokeratins in 7 of 8 cases (88%). Expression of low-molecular-weight cytokeratins and epithelial membrane antigen was limited, confined to only scattered cells in 7 of 8 (88%), and 4 of 8 (50%) of cases, respectively. Cytokeratin 7 expression was more widespread (7 of 8 cases, 88%). Cytokeratin 20 was negative. Expression of CD99 and bcl-2 was seen in 6 of 8 (75%) and 7 of 8 (88%) cases, respectively. CD117, INI-1, and TLE1 expression was seen in 6 of 8 (75%), 8 of 8 (100%), and 1 of 5 (20%) of cases, respectively. We conclude that traditional morphologic study and a limited panel of ancillary immunostains are sufficient for the distinction of SETTLE from synovial sarcoma in almost all instances. Molecular genetic study may, however, be helpful in selected cases, particularly in limited biopsies.
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PMID:Spindle epithelial tumor with thymus-like differentiation: a morphologic, immunohistochemical, and molecular genetic study of 11 cases. 1941 83