STAT6 is a human gene. The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein plays a central role in exerting IL4 mediated biological responses. It is found to induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. STAT6 protein expression can be identified by IHC in the cytoplasm and nucleus of several tissues.

Recurrent somatic fusions of the NGFI-A–binding protein 2 (NAB2) gene and STAT6 gene, located at chromosomal region 12q13, have been identified in Solitary Fibrous Tumors (SFT). In one study, Fifty-nine of 60 SFT cases (98%) showed nuclear expression of STAT6, which was usually diffuse and intense. All other tumor types of soft tumor tissues were negative for STAT6, except for three dedifferentiated Liposarcomas and one deep Fibrous Histiocytoma, which showed weak staining. STAT6 is a highly sensitive and specific immunohistochemical marker for SFT and can be helpful to distinguish this tumor type from histologic mimics. STAT6 is amplified in a subset of dedifferentiated Liposarcoma, resulting in STAT6 protein expression that can be detected by immunohistochemistry and may be a potential pitfall in the differential diagnosis of dedifferentiated Liposarcoma and Solitary Fibrous Tumor. These findings suggest a role for STAT6-mediated transcriptional activity in some cases of dedifferentiated Liposarcoma and highlight the genomic complexity and heterogeneity of dedifferentiated Liposarcomas.