All together, our data provide evidence that the abrogation of CD99 in EWS tumor cells leads to produce and release EXOs capable to transfer their antineoplastic effects into the nearby tumor cells, suggesting a novel atypical role for these microvesicles in reversion of malignancy rather than in priming the soil for progression and metastatic seeding.
A novel therapeutic combination of anti-CD99 diabody C7 and irinotecan was tested against two EW PDX; both drugs inhibited PDX growth, the addition of anti-CD99 was beneficial when chemotherapy alone was less effective.
Interestingly, a morphological and immunohistochemical overlap existed between <i>BCOR</i>-rearrangement tumor and <i>BCOR</i>-ITD-positive tumor, including areas with hypercellularity alternating with hypocellularity, a mixture of round cells and focal spindle cells, pale nuclear chromatin, inconspicuous nucleoli and abundant myxoid matrix, diffuse strong cyclin D1 expression, relatively strong expression of CD99 but lower than that in Ewing sarcoma, and a low Ki-67 proliferation index of about 10%.
In conclusion, the histopathological presence of Homer-Wright rosettes and immunohistochemical markers such as CD99, FLI-1 and CK are valuable factors for the diagnosis of ES, although cytogenetic analysis is considered the gold standard.
This study performed NKX2.2, TLE1, and CD99 immunohistochemistry in a group of EWS and SSs confirmed by reverse transcription-polymerase chain reaction to evaluate the utility of these novel markers in this context.
On balance, if the following features are seen: (1) a small round blue cell tumor with histomorphology more atypical than that of Ewing sarcoma, (2) cytoplasmic CD99 staining, nuclear WT1 positivity, negative keratin, desmin and myogenin; and (3) EWSR1 rearrangement negative by FISH, then molecular testing for CIC-DUX4 sarcoma should be considered.
CD99 immunoreactivity and low-level EWSR1 gene translocation by break-apart fluorescent in situ hybridization initially favored a diagnosis of Ewing sarcoma and chemotherapy commenced.
The study aim was to isolate and characterize CTCs in blood samples of Ewing sarcoma (ES) patients exploiting two main characteristics: CD99 expression and presence of chromosomal translocations.
Besides confirming the importance of CD99, our findings indicate that polymorphic variations in this gene may affect either development or progression of EWS, leading to further understanding of this cancer and development of better diagnostics/prognostics for children and adolescents with this devastating disease.
The goal of this work was to develop a rapid, inexpensive, and "up-scalable" process of a novel human bivalent single-chain fragment variable diabody (C7 dAbd) directed against CD99, as a new therapeutic approach for EWS.
CIC-DUX4 round cell sarcoma differs from Ewing sarcoma in that it has more atypical cytologic features and lacks the diffuse membranous CD99 staining pattern characteristic of Ewing sarcoma.
The strong IHC expression of SATB2 associated with CD99 immunonegativity and the absence of EWSR1 and FUS gene rearrangements in small cell osteosarcoma argues against the existence of a morphologic/genetic continuum with Ewing sarcoma.
The expression of the gene responsible of Ewing's sarcoma was inhibited at 78% ± 6% by associating the siRNA with the cd99-targeted nanoparticles compared with an inhibition of only 41% ± 9% achieved with the nontargeted nanoparticles.
It has been recently described that CD99 expression contributes to the Ewing tumor oncogenesis by modulating growth and differentiation of tumor cells.