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This Article Full Text Full Text (PDF) All Versions of this Article: jcp.2007.054262v1 jcp.2007.054262v2 61/6/744    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Google Scholar Articles by Vékony, H Articles by Bloemena, E PubMed PubMed Citation Articles by Vékony, H Articles by Bloemena, E

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

¹ Department of Oral and Maxillofacial Surgery/Oral Pathology, Academic Centre for Dentistry (ACTA), VU University Medical Center, Amsterdam, The Netherlands
² Crucell, Leiden, The Netherlands
³ Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
⁴ Netherlands Cancer Institute, Amsterdam, The Netherlands
⁵ Head and Neck Surgery/Otolaryngology, VU University Medical Center, Amsterdam, The Netherlands
⁶ Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

Correspondence to:
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

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, p16^INK4a, 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.