Determinants of variability of five programmed death ligand-1 immunohistochemistry assays in non-small cell lung cancer samples.

Programmed death ligand-1 (PD-L1) expression as determined by immunohistochemistry (IHC) is potentially predictive of clinical outcome. The aim of this study was to assess the concordance of reported PD-L1 IHC assays and investigate factors influencing variability. Consecutive sections from 20 non-small cell lung cancers (NSCLCs) comprising resection, core biopsy, cytology and pleural fluid samples underwent IHC with 5 different antibody/autostainer combinations: 22C3/Link48, 28-8/BOND-MAX, E1L3N/BOND-MAX, SP142/BenchMark and SP263/BenchMark.

Acquired resistance to PI3K/mTOR inhibition is associated with mitochondrial DNA mutation and glycolysis.

Acquired resistance (AQR) to drug treatment occurs frequently in cancer patients and remains an impediment to successful therapy. The aim of this study was to gain insight into how AQR arises following the application of PI3K/mTOR inhibitors. H1975 lung cancer cells with EGFR T790M mutations that confer resistance to EGFR inhibitors underwent prolonged treatment with the PI3K/mTOR inhibitor, BEZ235.

The Warburg effect and drug resistance.

: The Warburg effect describes the increased utilization of glycolysis rather than oxidative phosphorylation by tumour cells for their energy requirements under physiological oxygen conditions. This effect has been the basis for much speculation on the survival advantage of tumour cells, tumourigenesis and the microenvironment of tumours. More recently, studies have begun to reveal how the Warburg effect could influence drug efficacy and how our understanding of tumour energetics could be exploited to improve drug development.

Methodological aspects of whole-genome bisulfite sequencing analysis.

The combination of DNA bisulfite treatment with high-throughput sequencing technologies has enabled investigation of genome-wide DNA methylation beyond CpG sites and CpG islands. These technologies have opened new avenues to understand the interplay between epigenetic events, chromatin plasticity and gene regulation. However, the processing, managing and mining of this huge volume of data require specialized computational tools and statistical methods that are yet to be standardized.

RUNX3 downregulation in human lung adenocarcinoma is independent of p53, EGFR or KRAS status.

RUNX3 aberrations play a pivotal role in the oncogenesis of breast, gastric, colon, skin and lung tissues. The aim of this study was to characterize further the expression of RUNX3 in lung cancers. To achieve this, a lung cancer tissue microarray (TMA), frozen lung cancer tissues and lung cell lines were examined for RUNX3 expression by immunohistochemistry, while the TMA was also examined for EGFR and p53 expression.

Lack of RUNX3 inactivation in columnar cell lesions of breast.

Aims:   Ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) exhibit frequent RUNX3 inactivation by promoter hypermethylation and protein mislocalization. The aim of this study was to analyse columnar cell lesions (CCLs) to further characterize RUNX3 involvement in breast carcinogenesis.

Methods And Results:   RUNX3 expression and methylation was analysed by immunohistochemistry and methylation-specific polymerase chain reaction (PCR), respectively, in 75 CCLs.

Molecular-assisted immunohistochemical optimization.

Immunohistochemistry (IHC) is an essential tool in diagnostic surgical pathology, allowing analysis of protein subcellular localization. The use of IHC by different laboratories has lead to inconsistencies in published literature for several antibodies, due to either interpretative (inter-observer variation) or technical reasons. These disparities have major implications in both clinical and research settings.

TRARESA: a tissue microarray-based hospital system for biomarker validation and discovery.

Formalin fixed and paraffin embedded tissue (FFPE) collections in pathology departments are the largest resource for retrospective biomedical research studies. Based on the literature analysis of FFPE related research, as well as our own technical validation, we present the Translational Research Arrays (TRARESA), a tissue microarray centred, hospital based, translational research conceptual framework for both validation and/or discovery of novel biomarkers. TRARESA incorporates the analysis of protein, DNA and RNA in the same samples, correlating with clinical and pathological parameters from each case, and allowing (a) the confirmation of new biomarkers, disease hypotheses and drug targets, and (b) the postulation of novel hypotheses on disease mechanisms and drug targets based on known biomarkers.