Ki67, caspase-3 and M30 staining is absent in most tumour buds, suggesting decreased proliferation and apoptosis. However, the fact that Ki67 and caspase-3 immunoreactivity was associated with unfavourable prognosis points to a heterogeneous population of tumour buds.

Colorectal cancer is a heterogeneous disease at the histomorphological, clinical and molecular level. Approximately 20% of cases may progress through the "serrated" pathway characterized by BRAF mutation and high-level CpG Island Methylator Phenotype (CIMP). A large subgroup are additionally microsatellite instable (MSI) and demonstrate significant loss of tumor suppressor Cdx2. The aim of this study is to determine the specificity of Cdx2 protein expression and CpG promoter hypermethylation for BRAF V600E and high-level CIMP in colorectal cancer. Cdx2, Mlh1, Msh2, Msh6, and Pms2 were analyzed by immunohistochemistry using a multi-punch tissue microarray (TMA; n 5 220 patients). KRAS and BRAF V600E mutation analysis, CDX2 methylation and CIMP were investigated. Loss of Cdx2 was correlated with larger tumor size (P 5 0.0154), right-sided location (P 5 0.0014), higher tumor grade (P < 0.0001), more advanced pT (P 5 0.0234) and lymphatic invasion (P 5 0.0351). Specificity was 100% for mismatch repair (MMR)-deficiency (P < 0.0001), 92.2% (P < 0.0001) for BRAF V600E and 91.8% for CIMP-high. Combined analysis of BRAF V600E /CIMP identified Cdx2 loss as sensitive (80%) and specific (91.5%) for mutation/high status. These results were validated on eight well-established colorectal cancer cell lines. CDX2 methylation correlated with BRAF V600E (P 5 0.0184) and with Cdx2 protein loss (P 5 0.0028). These results seem to indicate that Cdx2 may play a role in the serrated pathway to colorectal cancer as underlined by strong relationships with BRAF V600E

The use of paraffin slides and tissue microarrays (TMA) is indispensable for translational research. However, storage of paraffin slides over time has a substantial detrimental effect on the quality and reliability of immunohistochemistry stains. Particularly affected by this issue may be any collaborative efforts where paraffin slides or TMAs are shipped to central laboratories and then ‘biobanked’ for some time until use. This article summarizes some of the key issues affecting loss of antigenicity on paraffin slides and some simple storage solutions to help maintain high quality immunohistochemistry results when paraffin slides must be stored for a certain time prior to use.

Low-serum high-density lipoprotein cholesterol in childhood is associated with an increased risk for asthma in adolescence, suggesting a potential role of this lipoprotein in the pathogenesis of paediatric asthma.

Unlike boys, girls with active asthma appear to be less active than their healthy peers, and this gender difference might explain the inconsistent evidence from previous reports on physical activity levels in asthmatic children. Further studies are needed to confirm the gender interaction in the childhood asthma-physical activity relation and the implications on current guidelines for physical exercise prescriptions in asthmatic children.