title: B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma.
abstract: Diffuse intrinsic pontine glioma (DIPG) is a brain cancer with a median survival of only 1 year. Lack of molecular characterization of this tumor impedes the development of novel therapies. Membrane protein B7-H3, aka CD276, involved in interactions with host defenses in certain cancers, has been shown to be over-expressed in the majority of malignant neuroectodermal tumors including adult high-grade glioma. Targeting B7-H3 with a monoclonal antibody has demonstrated safety and efficacy in the salvage treatment of stage IV childhood neuroblastoma, another neuroectodermal tumor. It thus stands to reason that B7-H3 might serve as a therapeutic target in DIPG. B7-H3 immunoreactivity was determined in DIPG and non-diffuse brainstem glioma specimens with immunohistochemistry. In addition, B7-H3 mRNA expression was evaluated with microarrays in another set of specimens. All of the nine (100 %) DIPG specimens were shown to be B7-H3 immunoreactive. In the non-diffuse brainstem glioma group, none of the eight WHO grade I specimens showed B7-H3 immunoreactivity and nine of the 24 WHO grade II specimens (37.5 %) showed B7-H3 immunoreactivity. The association between histological grade and B7-H3 immunoreactivity was statistically highly significant. B7-H3 mRNA expression was also significantly higher in DIPG samples than in normal brain and juvenile pilocytic astrocytoma (WHO grade I) specimens. In summary, B7-H3 is over-expressed in DIPG. Given the need for novel treatment in this disease, antibody-based immunotherapy against B7-H3 in DIPG warrants further investigation.
authors.affiliation: Department of Neurological Surgery, Weill Medical College of Cornell University, 1300 York Ave, Box 99, New York, NY 10065, USA. zhz2004@med.cornell.edu
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhou
authors.forename: Neal
authors.initials: N
authors.lastname: Luther
authors.forename: George M
authors.initials: GM
authors.lastname: Ibrahim
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.forename: Rajeev
authors.initials: R
authors.lastname: Vibhakar
authors.forename: Michael H
authors.initials: MH
authors.lastname: Handler
authors.forename: Mark M
authors.initials: MM
authors.lastname: Souweidane
mesh_terms: D060887:B7 Antigens / Q000235:genetics / Q000378:metabolism*; D020295:Brain Stem Neoplasms / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed
chemical_list: D060887:B7 Antigens; C423237:CD276 protein, human; D012333:RNA, Messenger