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Aims: Intraductal papillary neoplasm of the bile duct (IPNB) usually has a favourable prognosis, but occasionally is associated with invasive carcinoma. Overexpression of the polycomb group protein enhancer of zeste homolog 2 (EZH2) is involved in the progression of malignant tumours. In this study, we examined the significance of EZH2 expression in IPNB and its association with clinicopathological features and the expression of p16INK4a, p53 and mucin core proteins. Methods and results: We examined immunohistochemically the expression of EZH2, p16INK4a, MUC mucin core proteins and p53 in 15 patients with IPNB without invasion, including the cystic variant [male/female ratio (M/F) = 9/6], and in 19 with IPNB associated with invasive carcinoma (M/F = 13/6). The expression levels of EZH2, p53 and MUC1 were significantly lower ( P < 0.01), and of MUC6 were significantly higher ( P < 0.05), in IPNB without invasion than in IPNB with invasion. Expression of EZH2 was significantly correlated with expression of MUC1 ( P < 0.01) and inversely correlated with expression of MUC6 ( P < 0.05). In cholangiocarcinoma cells (HuCTT-1 and TFK-1), knockdown of EZH2 and MUC1 by small interfering RNA decreased invasion and proliferation, whereas knockdown of MUC6 increased invasion. Conclusions: Overexpression of EZH2 may be associated with malignant behaviour in IPNB in parallel with up-regulated MUC1 expression and down-regulated MUC6 expression. [ABSTRACT FROM AUTHOR]

Polycomb group (PcG) proteins play a role in the transcriptional repression of genes through histone modifications. Recent studies have clearly demonstrated that PcG proteins are required for the maintenance of embryonic as well as a broad range of adult stem cells, including hematopoietic stem cells (HSCs). PcG proteins maintain the self-renewal capacity of HSCs by repressing tumor suppressor genes and keep differentiation programs poised for activation in HSCs by repressing a cohort of hematopoietic developmental regulator genes via bivalent chromatin domains. Enforced expression of one of the PcG genes, Bmi1, augments the self-renewal capacity of HSCs. PcG proteins also maintain redox homeostasis to prevent premature loss of HSCs. These findings established PcG proteins as essential regulators of HSCs and underscored epigenetics as a new field of HSC research. In this review, we focus on the role of PcG proteins in the epigenetic regulation of the self-renewal capacity and multipotency of HSCs. [ABSTRACT FROM AUTHOR]

The article provides information on a study which assessed Bmil polycomb ring finger oncogene (Bmil) and enhancer of zeste homolog 2 (EZH2) protein expression in specimens of human nonsmall cell lung cancer (NSCLC). The study also investigated the association between Bmil and EZH2 proteins and several features, such as clinical and clinicopathologic parameters, cell biologic characteristics and patient outcomes. A detailed discussion the findings is presented.

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. [ABSTRACT FROM AUTHOR]