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IGF-1R is over-expressed in malignant tissue. IGF-1 is expressed at higher levels in ER positive tumours probably as a result of oestrogen stimulation while IGF-1R expression is higher in ER negative samples as an adaptation to lower local IGF-1 levels. An IGF-1 paracrine relationship may exist between tumour and ANCT but for STS and Cyp-19, there may be an autocrine-paracrine relationship. The IGF-1 ligand-receptor system is an important regulator of oestrogen production while oestrogen may be involved in stimulating IGF-1 expression. The expression of oestrogen synthesising enzymes is higher in ER negative breast cancers which may be due to the lack of oestrogen negative feedback or contribution from the overexpression of IGF-1R.

BackgroundSyk (Splenic Tyrosine Kinase) is an intracellular receptor protein kinase involved in cell proliferation, differentiation and phagocytosis. It has been studied in T and B lymphocytes, NK cells and platelets. The strong expression of Syk in mammary gland prompted research into its potential role in mammary carcinogenesis. There have been very few studies about its role in breast cancer with conflicting results. This study aims to investigate the hypothesis that Syk expression is down-regulated in breast cancer compared with ANCT and the association between its expression and clinicopathological parameters.Materials and methodsmRNA was extracted from 48 breast cancer specimens. Relative Syk to ribosomal RNA expression was determined by RT-PCR and Taqman methodology. Mann-Whitney U test was used to examine the association between Syk expression in cancer and ANCT. Spearman's rank correlation test was used to examine the association between Syk expression in tumours and patients' age, tumour size, tumour grade, estrogen and progesterone receptor status, lymph node metastasis, vascular invasion and clinical outcome.ResultsThe median for the relative value of Syk expression was 0.17 and 0.18 (range: 0.12 – 0.56 and 0.0 – 1.77) for tumours and ANCT respectively. There was no significant association between Syk expression in cancers and ANCT (p= 0.598) nor between Syk expression in tumours and patients' age, tumour size, tumour grade, estrogen and progesterone receptor status, lymph node metastasis, vascular invasion or prognosis.ConclusionThis study shows that Syk mRNA expression does not seem to vary between breast tumours and ANCT. Furthermore, we observed no significant association between Syk expression and clinicopathological parameters.

Background: Gene expression is stringently controlled under physiological conditions by epigenetic mechanisms, including the specific methylation of cytosine residues within CpG dinucleotides and orchestrated adjustments in the histone dependent organisation of chromatin. The organisation of DNA within the chromatin template depends upon highly conserved histone proteins, the properties of which continue to exceed the simplistic packaging role originally assigned to them. Histone modifier enzymes impart a dynamic histone code and specific permutations have significant implications for chromatin topology and the functional configuration of promoters. This study follows our initial report describing potential tumour suppressor function associated with the histone methyltransferase SETD2 in human breast cancer. The objective was to evaluate the expression profiles of sixteen additional histone modifier genes in women with primary operable breast cancer within a well annotated cohort with extended follow-up. Methods: Primary breast cancer tissues (n= 127) and adjacent benign/normal tissues (n=33) underwent RNA extraction and reverse transcription. The transcript levels of histone modifier genes were evaluated using real-time quantitative PCR, these included: histone acetyltransferases (CREBBP), Class 1 (HDAC1 and HDAC2), II (HDAC5) and III (SIRT1) histone deacetylases and histone methyltransferases (SUV39H1 and SUV39H2) amongst others. Transcript levels were analysed against a range of clinico-pathological variables, including: tumour size, grade, nodal involvement, histological subtype, receptor status, TNM stage, Nottingham Prognostic Index, disease free and overall survival over a 10 year follow-up period. Results: Transcript levels of the histone modifier genes in breast cancer tissues differed significantly from non-malignant samples (HDAC5, HDAC1, KDM4A and KDM6A). Amongst breast cancers, significant differences in transcript levels were associated with established pathological parameters and prognostic indices: tumour grade (KAT5, HDAC1, KDM4A, SUV39H1 and KDM6A), receptor status (KAT5, SMYD3 and KDM1A), histological type (KAT5, KDM5C, MYST1, KDM4A and MLL), TNM stage (SUV39H1, KAT2B, KDM1A, KDM4A, KDM5C, MYST1, HDAC5 and KAT5), Nottingham Prognostic Index (KDM5C, MLL, MYST1 and SMYD3), disease free survival (SUV39H1, SMYD3, HDAC5, KDM6A, HDAC1, KDM1A, KDM4A, MYST1, KDM5C, KAT5 and MLL) and overall survival (MYST1). Interestingly, significant correlations were also identified between the differential expression profiles of particular histone modifying genes. Conclusion: The expression profiles of histone modifier genes differ significantly between breast cancer tissues and normal/benign samples. Particular expression profiles in breast cancer are significantly associated with established pathological parameters, prognostic indices, disease free and overall survival. The biological significance and clinical relevance of altered expression of specific histone modifier genes and particular permutations of misexpression remain to be fully elucidated and further study is warranted. Epigenetic signatures derived from histone modifier genes may offer utility as biomarkers and histone modifier enzymes have potential for targeted therapeutic strategies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-05-05.

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