UPS is a diagnosis of exclusion (a diagnosis reached by the process of elimination) because the histopathology of this disorder's tumors is non-specific. UPS tumor cells are<unk>  (i.e. do not resemble any particular cell type) and<unk>  (i.e. highly variable in size, shape, and/or color) when examined microscopically. Therefore, the diagnosis of UPS is commonly based on detecting a specific set of proteins that are expressed by UPS tumor cells but not by the cells of other<unk>  and<unk>  tumors or visa versa (see Diagnosis section). A study of 52 individuals found that their UPS tumor cells expressed on their surface membranes PD-L1 protein (i.e. programmed death-ligand 1 protein) either focally (36.5% of cases) or strongly (9.62% of cases); 48.1% of these individuals had tumor cells which also expressed IDO1 protein (i.e. indoleamine 2,3-dioxygenase protein). Tumor cells that strongly expressed PD-L1 also expressed CMTM6 protein (i.e. CKLF like MARVEL transmembrane domain containing 6 protein). Strong PD‑L1 expression proved to be a poor, while expression of IDO‑1 proved to be a favorable, prognostic factor for disease outcomes. Individuals with tumor cells that strongly expressed CMTM6 protein also had poor prognoses. Increases in the expression of CMTM6 protein were associated in some cases with mutations that increased the number of copies of its gene, i.e. CMTM6. In a later study that examined 83 individuals, 72.8% had UPS tumor cells that expressed PD-L1 with 53%, 35%, and 12% of these cases showing weak, intermediate, and strong PD-L1 expression, respectively. And, in a study of 73 patients with UPS, 39 cases showed no, 23 cases showed low, 10 showed intermediate, and 11 strong immunoreactivity for AMPD2, i.e. 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. is responsible for production of) the retinoblastoma protein that functions as a tumor suppressor protein; 2) deletions and/or mutations in the TP53 gene that encodes tumor protein P53 (a protein which regulates cell proliferation and cell death); 3) mutations in the ATRX gene that encodes transcriptional regulator ATRX protein which contributes to regulating the expression of various genes; 4) mutations in the KMT2C gene which encodes lysine N-methyltransferase 2C protein (the KMT2C gene is mutated in various cancer types); 5) amplification of the IL7R gene which encodes Interleukin-7 receptor-α protein (mutations in the IL7R gene are commonly found in acute lymphoblastic leukemia) and 6) expression of a fusion gene (i.e. a hybrid gene formed from two previously independent genes as a result of a mutation) that merges TRIO with other genes and is often found in other<unk>  subtypes.)
Undifferentiated pleomorphic sarcoma
Low-grade fibromyxoid sarcoma
Solitary fibrous tumor
Sclerosing epithelioid fibrosarcoma
Myxoid liposarcoma
Angiomatoid fibrous histiocytoma
Myxoid tumor
Epithelioid sarcoma