Single-cell analysis reveals prognostic fibroblast subpopulations linked to molecular and immunological subtypes of lung cancer.

Fibroblasts are poorly characterised cells that variably impact tumour progression. Here, we use single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry (CIBERSORTx) to identify and characterise three major fibroblast subpopulations in human non-small cell lung cancer: adventitial, alveolar and myofibroblasts. Alveolar and adventitial fibroblasts (enriched in control tissue samples) localise to discrete spatial niches in histologically normal lung tissue and indicate improved overall survival rates when present in lung adenocarcinomas (LUAD).

Alternative tissue fixation for combined histopathological and molecular analysis in a clinically representative setting.

Formalin is the principal tissue fixative used worldwide for clinical and research purposes. Despite optimal preservation of morphology, its preservation of DNA and RNA is poor. As clinical diagnostics increasingly incorporates molecular-based analysis, the requirement for maintaining nucleic acid quality is of increasing importance.

The evolving role of image-guided biopsy and specimen fixation-update from an oncology setting.

Image-guided biopsy is well established in clinical practice, however a recent shift towards "personalized medicine" and genomic research, particularly in the oncology setting, has resulted in a greater demand for tissue, not only at preliminary diagnosis but at multiple time points in the patient's journey. Research into the molecular pathobiology underpinning cancer development and progression continues to identify diagnostic, predictive and prognostic biomarkers that help determine and guide treatment both at the outset, and as patient's progress or recur. This extensive tissue analysis however, necessitates larger tissue cores and a greater number of biopsies with correct fixation of the specimens obtained.

Somatic cancer genetics in the UK: real-world data from phase I of the Cancer Research UK Stratified Medicine Programme.

Introduction: Phase I of the Cancer Research UK Stratified Medicine Programme (SMP1) was designed to roll out molecular pathology testing nationwide at the point of cancer diagnosis, as well as facilitate an infrastructure where surplus cancer tissue could be used for research. It offered a non-trial setting to examine common UK cancer genetics in a real-world context.

Methods: A total of 26 sites in England, Wales and Scotland, recruited samples from 7814 patients for genetic examination between 2011 and 2013.

Crowdsourcing for translational research: analysis of biomarker expression using cancer microarrays.

Background: Academic pathology suffers from an acute and growing lack of workforce resource. This especially impacts on translational elements of clinical trials, which can require detailed analysis of thousands of tissue samples. We tested whether crowdsourcing - enlisting help from the public - is a sufficiently accurate method to score such samples.

Comparability of slack water and Lagrangian flow respirometry methods for community metabolic measurements.

Coral reef calcification is predicted to decline as a result of ocean acidification and other anthropogenic stressors. The majority of studies predicting declines based on in situ relationships between environmental parameters and net community calcification rate have been location-specific, preventing accurate predictions for coral reefs globally. In this study, net community calcification and production were measured on a coral reef flat at One Tree Island, Great Barrier Reef, using Lagrangian flow respirometry and slack water methods.

Evidence of mycobacterial disease in COPD patients with lung volume reduction surgery; the importance of histological assessment of specimens: a cohort study.

Background: Patients with COPD are at risk of non-tuberculous mycobacterial infection (NTM). This study examined the histology of lung tissue from COPD patients following lung volume reduction with particular focus on evidence of mycobacterial infection.

Methods: Retrospective histological study of 142 consecutive lung volume reduction surgical specimens (126 separate patients) at Royal Brompton Hospital between 2000 - 2013, with prospectively collected preoperative data on exacerbation rate, lung function and body mass index.

Anthropogenic changes to seawater buffer capacity combined with natural reef metabolism induce extreme future coral reef CO2 conditions.

Ocean acidification, via an anthropogenic increase in seawater carbon dioxide (CO2 ), is potentially a major threat to coral reefs and other marine ecosystems. However, our understanding of how natural short-term diurnal CO2 variability in coral reefs influences longer term anthropogenic ocean acidification remains unclear. Here, we combine observed natural carbonate chemistry variability with future carbonate chemistry predictions for a coral reef flat in the Great Barrier Reef based on the RCP8.

Stratified medicine for cancer therapy.

As knowledge of the biological processes underlying malignant transformation becomes increasingly sophisticated, apparently similar diseases can be redefined according to the critical disrupted biological pathways and networks. The key genetic changes in most cancers can be mapped to one of a relatively few pathways, making it possible to classify tumours by their abnormal pathways and to identify potentially treatable--'druggable'--targets within these. The aim of the stratified approach to cancer therapy is to improve the effectiveness, tolerability and affordability of novel therapeutic agents.

Observer agreement comparing the use of virtual slides with glass slides in the pathology review component of the POSH breast cancer cohort study.

Aims: (1) To compare the use of scanned virtual slide images (virtual microscopy) with glass slides (conventional microscopy) in the assessment of morphological characteristics of breast cancers within the setting of the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH), involving a cohort of women under 40 years of age, presenting with breast cancer. (2) To assess the acceptability to histopathologists of the use of virtual slide images.

Methods: 13 histopathologists from the UK and Australia participated in the POSH pathology review.