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Collectively, our findings suggest that the heterozygous mg�� mutation accelerates some aspects of vascular ageing and eventually leads to aortic manifestations resembling those of Marfan syndrome. Importantly, our data also indicate that vascular abnormalities in Fbn1 mice are opposite to those induced by elastin haploinsufficiency during ageing that affect blood pressure, vascular dimensions, and number of elastic lamellae. Copyright ? 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. ""There is an urgent need to improve prognostic classifiers in breast cancer. Ki67 and B-cell lymphoma 2 protein (BCL2) are established prognostic markers which have traditionally been assessed separately, in a dichotomous manner. This study was conducted to test the hypothesis that combinatorial assessment of these markers would Thymidine kinase provide superior prognostic information and improve their clinical utility. Tissue microarrays were used to assess the expression of Ki67 and BCL2 in 2749 cases of invasive breast cancer. We devised a Ki67/BCL2 index representing the relative expression of each protein and assessed its association with breast cancer-specific survival (BCSS) using a Cox proportional-hazards model. Based on our findings, an independent cohort of 3992 cases was used to validate the prognostic significance of the Ki67/BCL2 MK-8776 purchase index. All survival analyses were conducted on complete data as well as data where missing values were resolved using multiple imputation. This study complied with reporting recommendations for tumour marker prognostic studies (REMARK) criteria. The Ki67/BCL2 index showed a significant association with BCSS at 10 years in estrogen receptor (ER)-positive disease. In multivariate analysis, adjusting for major clinical and molecular markers, the Ki67/BCL2 index retained prognostic significance, robustly classifying cases into three risk groups [intermediate- versus low-risk hazard ratio (HR), 1.5; 95% confidence interval (95% CI), 1.0�C2.0; p = 0.031; high- versus low-risk HR, 2.6; 95% CI, 1.3�C5.0; p = 0.005]. This finding was validated in an independent selleck compound cohort of 3992 tumours containing 2761 ER-positive tumours (intermediate- versus low-risk HR, 1.7; 95% CI, 1.3�C2.1; p