A total of 11/13 of these malignant H3.3-mutant tumors exhibited an osteoclast-rich component: when imaging was available all but one presented at a subarticular site. Notably an additional 2 previously reported osteosarcomas with a p.G34R mutation were not immunoreactive for the antibody. Malignant bone tumors initially classified as osteosarcomas were the only other lesions (n=11) that showed G34W expression. If these sites were excluded from the analysis, H3.3 G34W expression was found in 97.8% of GCTB. This was not the case for the rare variants, p.G34L, M, and V, which occurred most commonly in the small bones of the hands, patella, and the axial skeleton. We also determined the incidence of H3.3 G34 mutations in primary malignant bone tumors as assessed by genotype and H3.3 G34W immunostaining. Having recently reported that H3.3 G34W mutations are characteristic of this tumor type, we have now investigated the sensitivity and specificity of the anti-histone H3.3 G34W rabbit monoclonal antibody in a wide variety of tumors including histologic mimics of GCTB to assess its value as a diagnostic marker. Giant cell tumor of bone (GCTB) is a locally aggressive subarticular tumor.
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Flanagan, MD, PhD, UCL Cancer Institute, Huntley Street, London WC1E 6BT, UK (e-mail: ).
The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.Ĭorrespondence: Adrienne M. was supported by the Gertrude von Meissner-Stiftung and the Basel Bone Tumour Reference Centre Foundation. was supported by the National Institute for Health Research, UCLH Biomedical Research Centre, and the UCL Experimental Cancer Centre. by the Royal National Orthopaedic Hospital NHS Trust NHS Trust, and the Skeletal Cancer Action Trust (Scat), UK. and A.M.F.: analysis of the data and writing of the manuscript.Ĭonflicts of Interest and Source of Funding: Supported by the Medical Research Council grant (MR/M00094X/1).
R.G., F.B., H.Y., M.G., and A.G.: performed immunohistochemistry and molecular testing. D.B.: reviewed the cases included from Basel. A.M.F., F.A., and R.T: review of slides and immunohistochemistry scoring. This product is not labeled for the use under discussion.Ī.M.F. The rabbit monoclonal anti-histone H3.3 G34W antibody (clone RM263) and the rabbit monoclonal histone H3F3 K36M antibody (clone RM193) were kindly provided as a gift by RevMAb Biosciences USA Inc. ‡Basel Bone Tumour Reference Centre (BBTRC), University Hospital Basel and University of Basel, Basel, Switzerland †Cancer Institute, University College London, London, UK *Royal National Orthopaedic Hospital NHS Trust, Stanmore, Greater London