In the new review all the tumors were re-classified as, ES (n=16), Ewing-like tumor with EWSR1 rearrangement and amplification and possible EWSR1-NFATC2 gene fusion (n=1), CIC-rearranged sarcomas or undifferentiated sarcoma, most consistent with CIC-rearranged sarcoma (n=7), sarcoma with BCOR-alteration or undifferentiated sarcoma, consistent with BCOR-associated sarcoma (n=3), neuroblastoma (n=2), unclassifiable neoplasm with neuroblastic differentiation (n=1), malignant rhabdoid tumor (n=2), lymphoblastic lymphoma (n=1), clear cell sarcoma of the gastrointestinal tract (n=1), small cell carcinoma (n=1), sclerosing rhabdomyosarcoma (n=1), desmoplastic small round cell tumor (n=1), malignant peripheral sheath nerve tumor (n=1), poorly-differentiated synovial sarcoma (n=1), Possible gastrointestinal stromal tumor/GIST with predominant round cells (n=1) and possible SMARCA4-deficient-sarcoma (n=1).
Primitive round- or spindle-cell EWSR1-negative undifferentiated sarcomas harboring CIC-DUX4 gene fusion are the most common form of Ewing-like sarcomas.
We observed an association between 17p deletions and tumor presentation being more frequent in recurrent and metastatic tumors than primary lesion. p53 nuclear overexpression was associated with tumor grade, size, and more frequently detected in metastatic than primary sarcomas.
Four years later in a second examination with molecular methods for a study of adrenal sarcomas, this diagnosis must be revised due to the lack of MDM-2 gene amplification and FKHR translocation which exclude sarcoma.
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) involved in the genesis of several human cancers; indeed, ALK was initially identified in constitutively activated and oncogenic fusion forms--the most common being nucleophosmin (NPM)-ALK--in a non-Hodgkin's lymphoma (NHL) known as anaplastic large-cell lymphoma (ALCL) and subsequent studies identified ALK fusions in the human sarcomas called inflammatory myofibroblastic tumors (IMTs).
Because anaplastic lymphoma kinase (ALK) translocation is common in sarcoma, ALK fluorescence in situ hybridization (FISH) was performed and the result was positive.
Mutations in the v-raf murine sarcoma viral oncogenes homolog B1 (BRAF) isoform of the RAF kinase or KRAS isoform of the RAS protein are found as activating mutations in approximately 30% of all human cancers.
We examined the effect of overexpression of p21(waf1) on cytotoxicity of paclitaxel, a microtubule stabilizer, using a tetracycline-inducible expression system in human sarcoma cells (SaOs-2) that lack both functional retinoblastoma protein and p53.
In details, activating epidermal growth factor receptor mutations were detected in 21 % of 311 evaluable patients, Kirsten rat sarcoma 2 viral oncogene homolog mutation in 22 % of the 77 evaluable patients and anaplastic lymphoma kinase translocations analysis was performed in 74 patients and resulted positive in 23 % of cases.
Many malignancies display amplification of MDM genes encoding negative regulators of p53 and therefore much effort to date has concentrated on the development of molecules that inhibit MDM2, the most advanced of which are being tested in clinical trials for sarcoma, glioblastoma, bladder cancer and lung adenocarcinoma.
We report here on the first set of ten such families, eight of which were identified through a proband with sarcoma. p53 exons 5 to 8 have been sequenced following polymerase chain reaction amplification performed on DNA isolated from total blood.
These results are in keeping with a "BCOR-alteration family" of renal and extrarenal neoplasms which includes CCSK and undifferentiated round cell sarcomas of soft tissue/primitive myxoid mesenchymal tumor of infancy (which typically harbor BCOR internal tandem duplication), and BCOR-CCNB3 sarcomas, all of which are primarily driven by BCOR overexpression and have overlapping (but not identical) clinicopathologic features.
A high proliferative index was demonstrated in 27.5% (11/40) of the tumours (2 MFH, 4 leiomyosarcomas, 1 rhabdomyosarcoma, 1 osteosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma). p53 overexpression was associated with high tumour grade (p < 0.05) and MIB-1 expression was correlated with reduced survival (p < 0.05), but p53 overexpression was not significantly associated with either MIB-1 score or with overall survival of the patients.
We evaluated BRG1 and INI1 expression in 12 SCCOHTs and in a series of 122 tumors that could mimic SCCOHT morphologically: 9 juvenile granulosa cell tumors, 47 adult granulosa cell tumors, 33 high-grade ovarian serous carcinomas, 9 desmoplastic round cell tumors, 13 Ewing sarcomas (5 from the pelvis and 8 from soft tissues), 1 round cell sarcoma associated with CIC-DUX4 translocation from soft tissue (thigh), 1 case of high-grade endometrial stromal sarcoma of the ovary, and 9 melanomas.
BCOR ITD were present in 1 uterine sarcoma diagnosed as HG-ESS and 2 undifferentiated sarcomas with uniform nuclear features, all of which lacked any of the recurrent chromosome translocations known to occur in ESS.
Tumor cells were diffusely positive for p53 and focally positive for epithelial markers and EGFR, but were negative for thyroid transcription factor-1, suggesting an initial diagnosis of primary pleomorphic sarcoma.
We performed mutational analysis of recurrent mutation sites of PIK3CA (exons 9 and 20), JAK2 (exon 14), BRAF (exon 15), FOXL2 (exon 1), IDH1 (exon 4), AKT1 (exon 3), and EZH2 (exon 16) genes in 108 sarcomas by single- strand conformation polymorphism and DNA sequencing.