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Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults.

ABSTRACT: GD2 and GD3 are the tumor-associated glycolipid antigens found in a broad spectrum of human cancers. GD2-specific antibody is currently a standard of care for high-risk neuroblastoma therapy. In this study, the pattern of GD2 and GD3 expression among pediatric/adolescent or young adult tumors was determined, providing companion diagnostics for targeted therapy.Ninety-two specimens of human osteosarcoma (OS), rhabdomyosarcoma (RMS), Ewing family of tumors, desmoplastic small round cell tumor (DSRCT), and melanoma were analyzed for GD2/GD3 expression by immunohistochemistry. Murine monoclonal antibody 3F8 was used for GD2 staining, and R24 for GD3. Staining was scored according to both intensity and percentage of positive tumor cells from 0 to 4.Both gangliosides were highly prevalent in OS and melanoma. Among other tumors, GD3 expression was higher than GD2 expression. Most OS samples demonstrated strong staining for GD2 and GD3, whereas expression for other tumors was highly variable. Mean intensity of GD2 expression was significantly more heterogeneous (P < 0.001) when compared to GD3 across tumor types. When assessing the difference between GD2 and GD3 expression in all tumor types combined, GD3 expression had a significantly higher score (P = 0.049). When analyzed within each cancer, GD3 expression was significantly higher only in DSRCT (P = 0.002). There was no statistical difference in either GD2 or GD3 expression between primary and recurrent sarcomas.GD2/GD3 expression among pediatric solid tumors is common, albeit with variable level of expression. Especially for patients with sarcoma, these gangliosides can be potential targets for antibody-based therapies.

SUBMITTER: Dobrenkov K

PROVIDER: S-EPMC5215083 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults.

Dobrenkov Konstantin K Ostrovnaya Irina I Gu Jessie J Cheung Irene Y IY Cheung Nai-Kong V NK

Pediatric blood & cancer 20160615 10

<h4>Background</h4>GD2 and GD3 are the tumor-associated glycolipid antigens found in a broad spectrum of human cancers. GD2-specific antibody is currently a standard of care for high-risk neuroblastoma therapy. In this study, the pattern of GD2 and GD3 expression among pediatric/adolescent or young adult tumors was determined, providing companion diagnostics for targeted therapy.<h4>Methods</h4>Ninety-two specimens of human osteosarcoma (OS), rhabdomyosarcoma (RMS), Ewing family of tumors, desmo ...[more]

PMID: 27304202

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Project description:Some subsets of pediatric sarcoma patients have very poor survival rates. We sought to determine the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric sarcoma populations with <25% predicted overall survival (OS). Patients with ultrahigh-risk Ewing's sarcoma family of tumors (ESFT), alveolar rhabdomyosarcoma, or desmoplastic small round cell tumors received EPOCH-fludarabine induction, a cyclophosphamide/fludarabine/melphalan preparative regimen, and HLA matched related peripheral blood stem cells. Thirty patients enrolled; 7 did not undergo alloHSCT because of progressive disease with diminishing performance status during induction. All 23 alloHSCT recipients experienced rapid full-donor engraftment, with no peritransplantation mortality. Five of 23 alloHSCT recipients (22%) remain alive (OS of 30% by Kaplan-Meier analysis at 3 years), including 3 of 7 (42%) transplanted without overt disease (median survival 14.5 versus 29.0 months from alloHSCT for patients transplanted with versus without overt disease, respectively). Among the 28 patients who progressed on the study, the median survival from date of progression was 1.9 months for the 7 who did not receive a transplant compared with 11.4 months for the 21 transplanted (P = .0003). We found prolonged survival after posttransplantation progression with several patients exhibiting indolent tumor growth. We also saw several patients with enhanced antitumor effects from posttransplantation chemotherapy (objective response to pretransplantation EPOCH-F was 24% versus 67% to posttransplantation EOCH); however, this was associated with increased toxicity. This largest reported series of alloHSCT in sarcomas demonstrates that alloHSCT is safe in this population, and that patients undergoing alloHSCT without overt disease show higher survival rates than reported using standard therapies. Enhanced chemo- and radiosensitivity of tumors and normal tissues was observed posttransplantation.

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Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults.

Publications

Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults.

Similar Datasets

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