EZH2 is a sensitive marker of malignancy in salivary gland tumors

BACKGROUND: The immunohistochemical detection of Enhancer of zeste homologue 2 (EZH2) proved to be a useful tool to recognize the malignant nature of tumors in a wide variety of neoplasms. The histological diagnostics of salivary gland tumors is a challenging task, and a reliable marker of malignancy would be extremely helpful. METHODS: EZH2 expression was investigated in 54 malignant and 40 benign salivary gland tumors of various histological types by standard immunohistochemistry. RESULTS: The majority (n = 52) of the malignant tumors stained positively, while all the investigated benign tumors were negative for EZH2. CONCLUSIONS: EZH2 expression in salivary gland tumors, similarly to the tumors of other organs is not characteristic for any tumor type, but is a solid marker of the malignant nature of the tumors

De relatie tussen zelfwaardering en gehechtheid aan ouders bij zevenjarige kinderen

In the present study, the effects of attachment relationships on 7-year-olds' selfesteem were examined. It was examined whether a secure representation of attachment has positive effects on children's self-esteem. Furthermore, the predictive value of attachment to father and mother was tested. It was examined what the effects are of a secure attachment relationship to one parent, but an insecure to the other, of two secure attachment relationships, and of two insecure attachment relationships. Seventy children (36 boys and 34 girls) participated in the study. Results show a relation between the representations of child-mother and child-father attachment and children's self-esteem. Children with a secure representation of attachment to mother or father show a more positive selfesteem (assessed by a Puppet Interview) than children with an insecure representation of attachment. This study is the first to show a relation between young children's self-esteem and the representation of attachment to father. When examining the joint effects of child-mother and child-father attachments, it was found that a secure attachment to one parent can compensate for an insecure attachment to the other parent

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC

Deregulated expression of p16INK4a and p53 pathway members in benign and malignant myoepithelial tumours of the salivary glands

Aims: Myoepithelial salivary gland tumours are uncommon and follow an unpredictable biological course. The aim was to examine their molecular background to acquire a better understanding of their clinical behaviour. Methods and results: Expression of protein (E2F1, p16INK4a, p53, cyclin D1, Ki67 and Polycomb group proteins BMI-1, MEL-18 and EZH2) was investigated in 49 benign and 30 primary malignant myoepithelial tumours and five histologically benign recurrences by immunohistochemistry and the findings correlated with histopathological characteristics. Benign tumours showed a higher percentage of cells with expression of p16INK4a pathway members [p16INK4a and E2F1 (both P < 0.001), and cyclin D1, P = 0.002] compared with normal salivary gland. Furthermore, malignant tumours expressed p53 (P = 0.003) and EZH2 (P = 0.09) in a higher percentage. Recurrences displayed more p53 + tumour cells (P = 0.02) than benign primaries. Amongst the benign tumours, the clear cell type had the highest proliferation fraction (P = 0.05) and a higher percentage of EZH2 was detected in the plasmacytoid cell type (P = 0.002). Conclusions: This study is the first to demonstrate that deregulation of the p16INK4a senescence pathway is involved in the development of myoepithelial tumours. We propose that additional inactivation of p53 in malignant primaries and benign recurrences contributes to myoepithelial neoplastic transformation and aggressive tumour growth

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

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