Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines.
A large necrotic tumour positive for CK 22, EMA, CD 99 and BCL-2 but negative for translocation in COBRA-FISH analysis by break-apart probe could be excised and revealed a very rare subtype of synovial sarcoma metastasis arising from the endocard of the left atrium.
Interestingly, whereas bcl2 over-expression appears to be restricted to the spindle cell tumoral component, c-kit mainly involves the epithelial component of biphasic SS.
The SYT-SSX fusion protein that results from the X,18 translocation is an appealing target, as are the proteins overexpressed in synovial sarcoma: bcl-2, EGFR, and HER-2/neu.
Four of 19 synovial sarcomas (21%) demonstrated nuclear over-expression of p53 protein; 18 of 19 tumors (94%) stained positive for Bcl-2; and 13 of 19 tumors (68%) were immunoreactive with EGFR.
In summary, avicin D selectively induced apoptosis, inhibited STAT-3 activation, and decreased apoptosis inhibitors (bcl-2 and survivin) in CTCL cell lines and SS patients' Sézary cells.
In addition to these cytogenetic changes, bcl-2 expression, as assessed by immunohistochemistry, has been reported to be an almost general constitutive alteration of SS.
Quisinostat inhibits aggresome formation in response to proteasome inhibition, and combination treatment leads to elevated endoplasmic reticulum stress, activation of pro-apoptotic effector proteins BIM and BIK, phosphorylation of BCL-2, increased levels of reactive oxygen species, and suppression of tumor growth in a murine model of synovial sarcoma.
Thus, the contributory role of BCL2 in synovial sarcomagenesis does not appear to render it as a therapeutic target, but mitochondrial antiapoptotic BCL2 family members may be.<b>Implications:</b> The association of BCL2 expression with synovial sarcoma is found to fit with a subtle, but significant, impact of its enhanced presence or absence during early tumorigenesis.
These tumors were subjected to methylation profiling and could be assigned to Ewing sarcoma in 14 (47%), to small blue round cell tumors with CIC alteration in 6 (20%), to small blue round cell tumors with BCOR alteration in 4 (13%), to synovial sarcoma and to malignant rhabdoid tumor in 2 cases each.
Furthermore, BCOR-rearranged tumors often displayed spindle cell areas, either well defined in intersecting fascicles or blending with the round cell component, which appears distinct from most other fusion-positive SBRCTs and shares histologic overlap with poorly differentiated synovial sarcoma.
BCOR-CCNB3-positive soft tissue sarcoma with round-cell and spindle-cell histology: a series of four cases highlighting the pitfall of mimicking poorly differentiated synovial sarcoma.
BCOR-CCNB3 fusion sarcoma is cyclin B3-positive, usually occurs in bone or soft tissue of children, and may mimic a poorly differentiated synovial sarcoma.
SS significantly upregulated glyoxalase 1 (Glo1) and NADPH quinine oxidoreductase 1 (NQO1) expression but reduced CML accumulation and downregulated receptor for AGEs (RAGE).