A Reliable Marker Defining Benign And Malignant Giant Cell Tumor ...

Trang chủ » H3.3 G34w » A Reliable Marker Defining Benign And Malignant Giant Cell Tumor ...

Có thể bạn quan tâm

Clipboard, Search History, and several other advanced features are temporarily unavailable. Skip to main page content Dot gov

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation pubmed logo Search: Search Advanced Clipboard User Guide Save Email Send to
  • Clipboard
  • My Bibliography
  • Collections
  • Citation manager
Display options Display options Format Abstract PubMed PMID

Save citation to file

Format: Summary (text) PubMed PMID Abstract (text) CSV Create file Cancel

Email citation

Email address has not been verified. Go to My NCBI account settings to confirm your email and then refresh this page. To: Subject: Body: Format: Summary Summary (text) Abstract Abstract (text) MeSH and other data Send email Cancel

Add to Collections

  • Create a new collection
  • Add to an existing collection
Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel

Add to My Bibliography

  • My Bibliography
Unable to load your delegates due to an error Please try again Add Cancel

Your saved search

Name of saved search: Search terms: Test search terms Would you like email updates of new search results? Saved Search Alert Radio Buttons
  • Yes
  • No
Email: (change) Frequency: Monthly Weekly Daily Which day? The first Sunday The first Monday The first Tuesday The first Wednesday The first Thursday The first Friday The first Saturday The first day The first weekday Which day? Sunday Monday Tuesday Wednesday Thursday Friday Saturday Report format: Summary Summary (text) Abstract Abstract (text) PubMed Send at most: 1 item 5 items 10 items 20 items 50 items 100 items 200 items Send even when there aren't any new results Optional text in email: Save Cancel

Create a file for external citation management software

Create file Cancel

Your RSS Feed

Name of RSS Feed: Number of items displayed: 5 10 15 20 50 100 Create RSS Cancel RSS Link Copy

Full text links

Wolters Kluwer full text link Wolters Kluwer Free PMC article Full text links

Actions

CiteCollectionsAdd to Collections
  • Create a new collection
  • Add to an existing collection
Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an errorPlease try again Add Cancel PermalinkPermalinkCopyDisplay options Display options Format AbstractPubMedPMID

Page navigation

  • Title & authors
  • Abstract
  • Conflict of interest statement
  • Figures
  • References
  • MeSH terms
  • Substances
  • Grants and funding
  • LinkOut - more resources
Title & authors Abstract Conflict of interest statement Figures References MeSH terms Substances Grants and funding LinkOut - more resources Full text links CiteDisplay options Display options Format AbstractPubMedPMID

Abstract

Giant cell tumor of bone (GCTB) is a locally aggressive subarticular tumor. 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. We also determined the incidence of H3.3 G34 mutations in primary malignant bone tumors as assessed by genotype and H3.3 G34W immunostaining. A total of 3163 tumors were tested. Totally, 213/235 GCTB (90.6%) showed nuclear H3.3 p.G34W immunoreactivity. 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. If these sites were excluded from the analysis, H3.3 G34W expression was found in 97.8% of GCTB. Malignant bone tumors initially classified as osteosarcomas were the only other lesions (n=11) that showed G34W expression. Notably an additional 2 previously reported osteosarcomas with a p.G34R mutation were not immunoreactive for the antibody. 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. We propose that subarticular primary malignant bone sarcoma with H3.3 mutations represent true malignant GCTB, even in the absence of a benign GCTB component.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest and Source of Funding: Supported by the Medical Research Council grant (MR/M00094X/1). A grant awarded to A.M.F. by the Royal National Orthopaedic Hospital NHS Trust NHS Trust, and the Skeletal Cancer Action Trust (Scat), UK. A.M.F. was supported by the National Institute for Health Research, UCLH Biomedical Research Centre, and the UCL Experimental Cancer Centre. D.B. was supported by the Gertrude von Meissner-Stiftung and the Basel Bone Tumour Reference Centre Foundation. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Figures

FIGURE 1

FIGURE 1

Photomicrographs (A and B) and…

FIGURE 1

Photomicrographs (A and B) and radiographs (C) of a GCTB with extensive secondary…

FIGURE 1 Photomicrographs (A and B) and radiographs (C) of a GCTB with extensive secondary aneurysmal bone cyst change, in areas indistinguishable from a primary aneurysmal bone cyst. H3.3 G34W is diffusely expressed by the stromal cells. D and E represent photomicrographs, of a different case (biopsy sample) showing a small isolated fragment of an osteoclast-rich lesion within blood clot. Strong H3.3 G34W (E) nuclei expression confirms the suspicion of a GCTB. The osteoclasts are negative for H3.3 G34W expression.
FIGURE 2

FIGURE 2

Photomicrographs of a malignant GCTB…

FIGURE 2

Photomicrographs of a malignant GCTB (M-07: initially classified as osteoclast-rich osteosarcoma) of the…

FIGURE 2 Photomicrographs of a malignant GCTB (M-07: initially classified as osteoclast-rich osteosarcoma) of the distal tibia showing morphologic variation including areas composed of epithelioid cells arranged in cords (A–C), osteoid deposition (B and C), tumor necrosis (C), and spindle cells with moderate nuclear atypia and numerous interspersed osteoclasts (D–F). Diffuse expression of H3.3 G34W is seen in the stromal cells (F).
FIGURE 3

FIGURE 3

A and B, Resection specimen…

FIGURE 3

A and B, Resection specimen and corresponding coronal T1 MRI scan showing a…

FIGURE 3 A and B, Resection specimen and corresponding coronal T1 MRI scan showing a lytic hemorrhagic lesion in the subarticular area of the distal femur with a surrounding low signal (sclerotic) component at the proximal aspect of the lesion. Photomicrographs of the subarticular component shows a conventional GCTB with diffuse H3.3 G34W expression (inset) (C). The proximal component comprises a bone-forming tumor with a spindle cell stroma showing a permeative growth pattern (D and E) (H3.3 G34W expression shown on inset D) case M10.
See this image and copyright information in PMC

References

    1. Athanasou NA, Bansal M, Forsyth R, et al. Fletcher C, Bridge J, Hogendoorn P, et al. Giant cell tumour of bone. WHO Classification of Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2013:321–324.
    1. Errani C, Ruggieri P, Asenzio MA, et al. Giant cell tumor of the extremity: a review of 349 cases from a single institution. Cancer Treat Rev. 2010;36:1–7. - PubMed
    1. Forsyth R, Jundt G.Fletcher CDM, Bridge JA, Hogendoorn PCW, et al. Giant cell lesion of the small bones. WHO Classification of Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2013:320.
    1. Song M, Zhang Z, Wu Y, et al. Primary tumors of the patella. World J Surg Oncol. 2015;13:163–176. - PMC - PubMed
    1. Al-Ibraheemi A, Inwards CY, Zreik RT, et al. Histologic spectrum of giant cell tumor (GCT) of bone in patients 18 years of age and below: a study of 63 patients. Am J Surg Pathol. 2016;40:1702–1712. - PubMed
Show all 25 references

MeSH terms

  • Adolescent Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Biomarkers, Tumor / genetics Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Bone Neoplasms / genetics* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Bone Neoplasms / pathology* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Female Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Giant Cell Tumor of Bone / genetics* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Giant Cell Tumor of Bone / pathology* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Histones / genetics* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Humans Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Immunohistochemistry Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Male Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Mutation* Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Reproducibility of Results Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search

Substances

  • Biomarkers, Tumor Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • H3-3A protein, human Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search
  • Histones Actions
    • Search in PubMed
    • Search in MeSH
    • Add to Search

Grants and funding

  • G0701018/MRC_/Medical Research Council/United Kingdom
  • G1100578/MRC_/Medical Research Council/United Kingdom
  • MR/M00094X/1/MRC_/Medical Research Council/United Kingdom
  • MR/N004272/1/MRC_/Medical Research Council/United Kingdom

LinkOut - more resources

  • Full Text Sources

    • Europe PubMed Central
    • Ingenta plc
    • Ovid Technologies, Inc.
    • PubMed Central
    • Wolters Kluwer

  • Other Literature Sources

    • scite Smart Citations

  • Medical

    • MedlinePlus Health Information
Full text links [x] Wolters Kluwer full text link Wolters Kluwer Free PMC article [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Send To
  • Clipboard
  • Email
  • Save
  • My Bibliography
  • Collections
  • Citation Manager
[x]

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Từ khóa » H3.3 G34w