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 sarcoma subtypes.) Diagnosis
The diagnosis of UPS depends on finding non-specific, undifferentiated tumor cells that have features suggestive of UPS and not features of other tumor types that also consist of pleomorphic, undifferentiated cells. The features primarily involve the expression of certain proteins by the tumor cells. The identifying proteins for UPS tumor cells are given in the preceding section. Identification proteins for tumors that have been confused with UPS inlclude:
Pleomorphic leimyosarcoma: Desmin and h-caldesmon (i.e. high molecular form of caldesmon.) proteins
Pleomorphic rhabdomyosarcoma: Desmin and myogenin proteins. Defifferentiated liposarcoma: MDM2 and CDK4 proteins. Poorly differentiated carcinoma (i.e.
A standard chemotherapy two-drug regimen (epirubicin plus ifosfamide) may be used in these cases. In place or combined with surgery and/or radiotherapy, severe and/or metastatic cases of UPS are commonly treated with epirubicin plus ifosfamide; doxorubicin alone or combined with ifosfamide, olaratumab, trabectedin, gemcitabine, or docetaxel;  cyclophosphamide, vincristine, doxorubicin, plus dacarbazine or cisplatin; cyclophosphamide, doxorubicin, plus dacarbazine; high dose methotrexate; or etoposide, ifosfamide, and cisplatin. These treatment regimens have been reported to lower local recurrence rates, prolong disease-free survival rates (i.e. time after treatment when no disease is detected), and increase overall survival rates (i.e. time after treatment to death from any cause). However, other studies report that the addition of radiotherapy and/or chemotherapy to surgical resection does not improve recurrence or overall survival rates; addition of radiotherapy to surgery improves local control of UPS tumors but not disease-free survival rates (i.e. time from treatment to recurrence of disease); and adjuvant chemotherapy and radiotherapy have no significant effects on local recurrence-free survival rates, metastasis-free survival times, and overall survival rates. Further studies are needed to define the best treatments for UPS tumors.In a retrospective study of 176 patients with localized UPS undergoing curative-intent treated with surgical resection or resection plus adjuvant treatment, disease-free survival rates at 120 months for patients with tumors in an extremity (leg or arm), heat/neck area, thorax, and abdomen/pelvis were about 70, 60, 50, and 0%, respectively; overall survival rates at 150 months for disease at these sites were about 90, 80, 75, and 35%, respectively.