e-Learning for Instruction and to Improve Reproducibility of Scoring Tumor-Stroma Ratio in Colon Carcinoma: Performance and Reproducibility Assessment in the UNITED Study.

Background: The amount of stroma in the primary tumor is an important prognostic parameter. The tumor-stroma ratio (TSR) was previously validated by international research groups as a robust parameter with good interobserver agreement.

Objective: The Uniform Noting for International Application of the Tumor-Stroma Ratio as an Easy Diagnostic Tool (UNITED) study was developed to bring the TSR to clinical implementation.

The prognostic value of the tumor-stroma ratio in squamous cell lung cancer, a cohort study.

Objectives: The tumor-stroma ratio (TSR) is based on the relative amount of stroma in the primary tumor and has proven to be an independent prognostic factor in various solid tumors. The prognosis of patients and adjuvant treatment decision making in lung squamous cell carcinomas (SqCC) is based on the TNM classification. Currently, no other prognostic biomarkers are available.

Tumour-stroma ratio has poor prognostic value in non-pedunculated T1 colorectal cancer: A multi-centre case-cohort study.

Background: Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in over-treatment of a large (>80%) proportion of T1 colorectal cancer patients. The tumour-stroma ratio (TSR), which is a measure for the relative amount of desmoplastic tumour stroma, is reported to be a strong independent prognostic factor in advanced-stage colorectal cancer, with a high stromal content being associated with worse prognosis and survival. We aimed to investigate whether the TSR predicts clinical outcome in patients with non-pedunculated T1 colorectal cancer.

Correlation of the tumour-stroma ratio with diffusion weighted MRI in rectal cancer.

Objective: This study evaluated the correlation between intratumoural stroma proportion, expressed as tumour-stroma ratio (TSR), and apparent diffusion coefficient (ADC) values in patients with rectal cancer.

Methods: This multicentre retrospective study included all consecutive patients with rectal cancer, diagnostically confirmed by biopsy and MRI. The training cohort (LUMC, Netherlands) included 33 patients and the validation cohort (VHIO, Spain) 69 patients.

The significance of stromal collagen organization in cancer tissue: An in-depth discussion of literature.

It has become clear that carcinogenesis goes beyond tumor cell biology. Cancer research has acknowledged the importance of biological functions of the tumor-microenvironment, wherein not only cellular components seem to hold valuable information but also structural components like collagen fibers. Several studies have focused on the significance of stromal collagen fiber organization and reported on its role in cancer progression, invasiveness and treatment response.

High Growth Rate of Pancreatic Ductal Adenocarcinoma in Mutation Carriers.

- mutation carriers have a 20% to 25% risk of developing pancreatic ductal adenocarcinoma (PDAC). Better understanding of the natural course of PDAC might allow the surveillance protocol to be improved. The aims of the study were to evaluate the role of cystic precursor lesions in the development of PDAC and to assess the growth rate.

Predictive potential of tumour-stroma ratio on benefit from adjuvant bevacizumab in high-risk stage II and stage III colon cancer.

Background: The tumour-stroma ratio (TSR) has proven to be an independent prognostic factor in colon cancer.

Methods: Haematoxylin eosin tissue slides of patients from the AVANT trial were microscopically scored for TSR and categorised as stroma -low or stroma -high. Scores were correlated to the primary and secondary endpoint disease-free survival (DFS) and overall survival (OS).

Breast Cancer Survival of BRCA1/BRCA2 Mutation Carriers in a Hospital-Based Cohort of Young Women.

Background: The primary aim of the study was to investigate prognosis and long-term survival in young breast cancer patients with a BRCA1 or BRCA2 germline mutation compared with noncarriers. The secondary aim was to investigate whether differences in survival originate from associations with tumor characteristics, second cancers, and/or treatment response.

Methods: We established a cohort of invasive breast cancer patients diagnosed younger than age 50 years in 10 Dutch hospitals between 1970 and 2003.

Locally Advanced Colon Cancer: Evaluation of Current Clinical Practice and Treatment Outcomes at the Population Level.

The goal of this study was to evaluate current clinical practice and treatment outcomes regarding locally advanced colon cancer (LACC) at the population level. Data were used from the Dutch Surgical Colorectal Audit from 2009 to 2014. A total of 34,527 patients underwent resection for non-LACC and 6,918 for LACC, which was defined as cT4 and/or pT4 stage.

Randomized Phase III Study to Assess Efficacy and Safety of Adjuvant CAPOX with or without Bevacizumab in Patients after Resection of Colorectal Liver Metastases: HEPATICA study.

Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF). Recurrence after resection of colorectal liver metastases (CRLMs), presumably caused by VEGF-mediated outgrowth of micrometastases, might decrease when VEGF is inhibited. This study examines the efficacy and safety of adding bevacizumab to an adjuvant regimen of CAPOX in patients undergoing radical resection for their CRLMs.

Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21.

There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants.

Hospital costs of colorectal cancer surgery for the oldest old: A Dutch population-based study.

Unlabelled: Background Due to increasing healthcare costs, discussions regarding increased hospital costs when operating on high-risk patients is rising. Therefore, the aim of this study was to analyze if oldest-old colorectal cancer patients have a greater impact on hospital costs than their younger counterparts.

Methods: All colorectal cancer procedures performed in 29 Dutch hospitals between 2010 and 2012 and listed in the Dutch Surgical Colorectal Audit were analyzed.

Prognostic value of automated KI67 scoring in breast cancer: a centralised evaluation of 8088 patients from 10 study groups.

Background: The value of KI67 in breast cancer prognostication has been questioned due to concerns on the analytical validity of visual KI67 assessment and methodological limitations of published studies. Here, we investigate the prognostic value of automated KI67 scoring in a large, multicentre study, and compare this with pathologists' visual scores available in a subset of patients.

Methods: We utilised 143 tissue microarrays containing 15,313 tumour tissue cores from 8088 breast cancer patients in 10 collaborating studies.

High-Throughput and High-Sensitivity Mass Spectrometry-Based N-Glycomics of Mammalian Cells.

The current protocols for glycomic analysis of cells often require a large quantity of material (5-20 million cells). In order to analyze the N-glycosylation from small amounts of cells (≤1 million) as obtained from, for example, primary cell lines or cell sorting, and in a higher throughput approach, we set up a robust 96-well format PVDF-membrane based N-glycan release protocol followed by linkage-specific sialic acid stabilization, cleanup, and MALDI-TOF-MS analysis. We further evaluated the influence of PNGase F incubation time on the N-glycan profile.

Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation.

Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER) breast cancer (per-g allele OR ER = 1.

High-throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium.

Automated methods are needed to facilitate high-throughput and reproducible scoring of Ki67 and other markers in breast cancer tissue microarrays (TMAs) in large-scale studies. To address this need, we developed an automated protocol for Ki67 scoring and evaluated its performance in studies from the Breast Cancer Association Consortium. We utilized 166 TMAs containing 16,953 tumour cores representing 9,059 breast cancer cases, from 13 studies, with information on other clinical and pathological characteristics.

Differences between colon and rectal cancer in complications, short-term survival and recurrences.

Purpose: Many apparent differences exist in aetiology, genetics, anatomy and treatment response between colon cancer (CC) and rectal cancer (RC). This study examines the differences in patient characteristics, prevalence of complications and their effect on short-term survival, long-term survival and the rate of recurrence between RC and CC.

Methods: For all stage II-III CC and RC patients who underwent resection with curative intent (2006-2008) in five hospitals in the Netherlands, occurrence of complications, crude survival, relative survival and recurrence rates were compared.

Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section.

On-tissue digestion matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can be used to record spatially correlated molecular information from formalin-fixed, paraffin-embedded (FFPE) tissue sections. In this work, we present the in situ multimodal analysis of N-linked glycans and proteins from the same FFPE tissue section. The robustness and applicability of the method are demonstrated for several tumors, including epithelial and mesenchymal tumor types.

Reduced 30-Day Mortality After Laparoscopic Colorectal Cancer Surgery: A Population Based Study From the Dutch Surgical Colorectal Audit (DSCA).

Objectives: To evaluate the impact of a laparoscopic resection on postoperative mortality after colorectal cancer surgery.

Background: The question whether laparoscopic resection (LR) compared with open surgery [open resection (OR)] for colorectal cancer influences the risk of postoperative mortality remains unresolved. Several meta-analyses showed a trend but failed to reach statistical significance.

Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers.

Purpose: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC.

Patients And Methods: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay.

Application of a Serum Protein Signature for Pancreatic Cancer to Separate Cases from Controls in a Pancreatic Surveillance Cohort.

Background: Pancreatic cancer (PC) surveillance is currently offered to individuals with a genetic predisposition to PC, but routinely used radiological screening modalities are not entirely reliable in detecting early-stage PC or its precursor lesions. We recently identified a discriminating PC biomarker signature in a sporadic patient cohort. In this study, we investigated if protein profiling can accurately distinguish PC from non-PC in a pancreatic surveillance cohort of genetically predisposed individuals.

Linkage-Specific in Situ Sialic Acid Derivatization for N-Glycan Mass Spectrometry Imaging of Formalin-Fixed Paraffin-Embedded Tissues.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging is a rapidly evolving field in which mass spectrometry techniques are applied directly on tissues to characterize the spatial distribution of various molecules such as lipids, protein/peptides, and recently also N-glycans. Glycans are involved in many biological processes and several glycan changes have been associated with different kinds of cancer, making them an interesting target group to study. An important analytical challenge for the study of glycans by MALDI mass spectrometry is the labile character of sialic acid groups which are prone to in-source/postsource decay, thereby biasing the recorded glycan profile.

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

Background: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction.

Genetic predisposition to ductal carcinoma in situ of the breast.

Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci.