rss
J Clin Pathol 2008;61:744-749 doi:10.1136/jcp.2007.054262
  • Original article

High expression of Polycomb group protein EZH2 predicts poor survival in salivary gland adenoid cystic carcinoma

  1. H Vékony1,
  2. F M Raaphorst2,
  3. A P Otte3,
  4. M van Lohuizen4,
  5. C R Leemans5,
  6. I van der Waal1,
  7. E Bloemena1,6
  1. 1
    Department of Oral and Maxillofacial Surgery/Oral Pathology, Academic Centre for Dentistry (ACTA), VU University Medical Center, Amsterdam, The Netherlands
  2. 2
    Crucell, Leiden, The Netherlands
  3. 3
    Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
  4. 4
    Netherlands Cancer Institute, Amsterdam, The Netherlands
  5. 5
    Head and Neck Surgery/Otolaryngology, VU University Medical Center, Amsterdam, The Netherlands
  6. 6
    Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
  1. Miss H Vékony, Department of Oral and Maxillofacial Surgery/Oral Pathology, Academic Centre for Dentistry (ACTA), VU University Medical Center (VUmc), Amsterdam, The Netherlands; h.vekony{at}vumc.nl
  • Accepted 24 January 2008
  • Published Online First 6 March 2008

Abstract

Background: The prognosis of adenoid cystic carcinoma (ACC), a malignant salivary gland tumour, depends on clinicopathological parameters. To decipher the biological behaviour of ACC, and to identify patients at risk of developing metastases, additional markers are needed.

Methods: Expression of the cell cycle proteins p53, cyclin D1, p16INK4a, E2F1 and Ki-67, together with the Polycomb group (PcG) proteins BMI-1, MEL-18, EZH2 and EED was investigated immunohistochemically 21 formalin-fixed, paraffin-embedded primary ACCs in relation to tumour characteristics.

Results: ACC revealed significantly increased expression of the cell cycle proteins compared to normal salivary tissue (n = 17). Members of the two PcG complexes displayed mutually exclusive expression in normal salivary gland tissue, with BMI-1 and MEL-18 being abundantly present. In ACC, this expression pattern was disturbed, with EZH2 and EED showing significantly increased expression levels. In univariate analysis, presence of recurrence, poor differentiation and high EZH2 levels (>25% immunopositivity) significantly correlated with unfavourable outcome. ACCs with high proliferative rate (>25% Ki-67 immunopositivity) significantly correlated with high levels of EZH2 and p16. Only the development of recurrence was an independent prognostic factor of survival in multivariate analysis.

Conclusions: Expression of PcG complexes and of essential cell cycle proteins is highly deregulated in ACC. Also, EZH2 expression has prognostic relevance in this malignancy.

Footnotes

  • Competing interests: None.

  • Funding: This work was supported by a grant from the Interuniversity Research School (IOT), Amsterdam, The Netherlands.

This Article

  1. Abstract
  2. Full text
  3. PDF
  4. All versions of this article:
    1. jcp.2007.054262v1
    2. jcp.2007.054262v2
    3. 61/6/744 most recent

Responses

  1. Submit a response
  2. No responses published

Register for free content


Free trial
Individuals may register for a free 60 day online trial to all content.

Free archive
The full back archive is now available for all BMJ Journals. Institutional subscribers may access the entire archive as part of their subscription. Personal subscribers will also have access to all content when logged in. Non-subscribers who register have free access to all articles published before 2006 right back to volume 1 issue 1. Register here to access the free archive of all BMJ Journals.

Don't forget to sign up for content alerts so you keep up to date with all the articles as they ar