Stem cell transcription factor SOX2 in synovial sarcoma and other soft tissue tumors

Zayed, Hebatalla GND

Soft tissue tumors, as an important oncology domain, entail different entities and are challenging regarding diagnosis and therapy. Here, we focused on synovial sarcoma alongside with other soft tissue tumors and specifically analyzed the expression and amplification of the gene SOX2 which has the full name SRY (sex determining region Y)-box2. SOX2 is a transcription factor responsible for the pluripotency of undifferentiated embryonic stem cells, promoting cellular proliferation and promoting invasion, migration and metastases in melanoma and other tumors. We also tested AntiHistone H3-trimethyl K27 (H3K27me3) expression in SOX2 positive cases in an attempt to correlate SOX2 gene expression with the posttranslational protein modification H3K27me3, both of which having been associated with stemness features of cancer cells. In our study, we included all samples (n=60) of synovial sarcoma at the Friedrich-Schiller University hospital of Jena (Germany) between January 2013 and December 2015 in a retrospective observational manner. We excluded cases whose histopathological material was not available anymore in the institute (n=6) and cases (n=4) whose paraffin block was not optimal for further investigation. Clinicopathological and Immunohistochemical analysis were performed by our institutional pathology team according to standard diagnostic protocols e.g. using antibodies against EMA, Bcl2, PanCK, CK7, CD34, Ki67 and S100. Molecular confirmation of the diagnosis was routinely performed by FISH and/or PCR to detect the t(x;18) translocation. We also employed tissue microarrays of different soft tissue tumors to compare the expression in synovial sarcoma with other sarcoma entities. Results were collected, tabulated and statistically analyzed. About 60 % of all synovial sarcoma cases were positive to Sox2. Meanwhile out of 343 soft tissue tumors, varying from nodular fasciitis to undifferentiated pleomorphic sarcoma, only 13 cases (3.8%) were Sox2 positive. Of these, 11 (84.6%) were undifferentiated high grade pleomorphic sarcoma. Out of 35 Sox2 positive synovial sarcoma cases, 25 (71, 4%) were H3K27me3 positive and 10 (28, 6%) were negative. SOX2 amplification was not detectable in 6 randomly chosen synovial sarcoma cases showing SOX2 protein expression. Sox2, a principal stem-cell transcription factor, is evidently involved in the tumorigenesis of many tumor entities. In soft tissue tumors, however, expression is largely restricted to synovial sarcoma. Immunohistochemical detection of SOX2 can thus help in the diagnostic challenge in differentiating synovial sarcoma from other soft tissue tumors. H3K27me3 was also found to be positive in the majority of Sox2-positive synovial sarcomas and this correlates with the idea that these tumors might have a pluripotent cell population as tumor-initiating cells. We think that this finding supports the hypothesis of synovial sarcoma as product of pluripotent mesenchymal stem cell populations rather than being derived from mutations in terminally differentiated cells. The results may add to the diagnostic scheme for synovial sarcoma diagnosis. Moreover, Sox2 might reveal a molecular approach in cancer treatment, namely by targeting epigenetic modulators that seems to play a role in SOX2 gene regulation.

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Zayed, Hebatalla: Stem cell transcription factor SOX2 in synovial sarcoma and other soft tissue tumors. Jena 2019.

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