AMP deaminase 2 protein; the gains in AMPD2 protein immunoreactivity were associated with copy number gains in the AMPD2 gene and patients with higher AMPD2 levels had poorer prognoses (5 year survivals for AMPD2 positive versus AMPD2 negative cases were ~38 and 59%, respectively). Other abnormalities found in some or isolated cases of UPS include: 1) Amplification of the Hippo signaling pathway, an intracellular cell signaling pathway that regulates cell proliferation and cell death; this amplification is associated with the overexpression of two proteins, vestigial-like family member 3 protein, a product of the VGLL3 gene, and YAP1, i.e. yes-associated protein 1, a product of the YAP1 gene, in the Hippo signaling pathway; 2) Abnormal activation of notch signaling pathways (this activation has been shown to promote the growth and survival of various types of cancer cells; and 3) Overexpression of DKK1, i.e. Dickkopf-related protein 1 (elevated in the tumor cells of various cancer types).UPS tumors also show gene and chromosome abnormalities that further studies may find contribute to the development and/or progression of UPS. These abnormalities, which have not yet been reported to be helpful in diagnosing UPS, include the following. 1) Deletion and/or inactivation or the RB1 gene that encodes (i.e.
This inhibition blocks the PD-L1 and PL-L2 ligands located on the surface of normal tissue cells from binding to PD-1 receptors on activated T-cells and thereby blocks the T-cells from organizing an inflammatory response that kills the normal cells. Tumor cells may use this inflammation-evading tactic: they may express PD-L1/PD-L2 and thereby block the T-cell-mediated immune responses to them (see Immune checkpoint). From ~47% to ~73% of UPS cases contain tumor cells that express PD-L1. In a retrospective review of 10 patients with UPS, 1 patient had a complete response, 3 had partial responses, and 6 had no response to pembrolizumab. (Further studies of the 4 pembrolizumab-responsive patients indicated that their tumor cells expressed PD-L1 in two cases but not in the other two cases.) In a retrospective study of 25 patients (21 patients treated with pembrolizumab, 4 treated with other immunotherapy agents), 7 attained stable disease, 7 attained partial responses, and 1 attained a complete response. In a study of 16 patients with UPS, 5 achieved short-term (lasting 1.2 to 1.4 months) stable disease in response to a regimen of pembrolizumab combined with the chemotherapy drug, cyclophosphamide. It is clear that new treatment strategies as well as further studies on the efficacy of pembrolizumab and similarly acting immunotherapy drugs used with or without radiotherapy and/or chemotherapy over longer time periods are needed to evaluate their usefulness in treating UPS. References


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