Self-Supervised Learning Reveals Clinically Relevant Histomorphological Patterns for Therapeutic Strategies in Colon Cancer.

Self-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-and-eosin-stained whole-slide images (WSIs). We trained an SSL Barlow Twins-encoder on 435 TCGA colon adenocarcinoma WSIs to extract features from small image patches. Leiden community detection then grouped tiles into histomorphological phenotype clusters (HPCs).

Serum -Glycosylation RPLC-FD-MS Assay to Assess Colorectal Cancer Surgical Interventions.

A newly developed analytical strategy was applied to profile the total serum -glycome of 64 colorectal cancer (CRC) patients before and after surgical intervention. In this cohort, it was previously found that serum -glycome alterations in CRC were associated with patient survival. Here, fluorescent labeling of serum -glycans was applied using procainamide and followed by sialic acid derivatization specific for α2,6- and α2,3-linkage types via ethyl esterification and amidation, respectively.

Tumour-stroma ratio (TSR) in breast cancer: comparison of scoring core biopsies versus resection specimens.

Purpose: Tumour-stroma ratio (TSR) is an important prognostic and predictive factor in several tumour types. The aim of this study is to determine whether TSR evaluated in breast cancer core biopsies is representative of the whole tumour.

Method: Different TSR scoring methods, their reproducibility, and the association of TSR with clinicopathological characteristics were investigated in 178 breast carcinoma core biopsies and corresponding resection specimens.

LncRNA LITATS1 suppresses TGF-β-induced EMT and cancer cell plasticity by potentiating TβRI degradation.

Epithelial cells acquire mesenchymal phenotypes through epithelial-mesenchymal transition (EMT) during cancer progression. However, how epithelial cells retain their epithelial traits and prevent malignant transformation is not well understood. Here, we report that the long noncoding RNA LITATS1 (LINC01137, ZC3H12A-DT) is an epithelial gatekeeper in normal epithelial cells and inhibits EMT in breast and non-small cell lung cancer cells.

Differential optineurin expression controls TGFβ signaling and is a key determinant for metastasis of triple negative breast cancer.

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat due to its aggressive characteristics and low response to the existing clinical therapies. Distant metastasis is the main cause of death of TNBC patients. Better understanding of the mechanisms underlying TNBC metastasis may lead to new strategies of early diagnosis and more efficient treatment.

Deep learning based tumor-stroma ratio scoring in colon cancer correlates with microscopic assessment.

Background: The amount of stroma within the primary tumor is a prognostic parameter for colon cancer patients. This phenomenon can be assessed using the tumor-stroma ratio (TSR), which classifies tumors in stroma-low (≤50% stroma) and stroma-high (>50% stroma). Although the reproducibility for TSR determination is good, improvement might be expected from automation.

Development of Tier 2 LC-MRM-MS protein quantification methods for liquid biopsies.

In the pursuit of personalized diagnostics and tailored treatments, quantitative protein tests contribute to a more precise definition of health and disease. The development of new quantitative protein tests should be driven by an unmet clinical need and performed in a collaborative effort that involves all stakeholders. With regard to the analytical part, mass spectrometry (MS)-based platforms are an excellent tool for quantification of specific proteins in body fluids, for example focused on cancer.

Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients.

The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients.

Longitudinal Serum Protein Analysis of Women with a High Risk of Developing Breast Cancer Reveals Large Interpatient Versus Small Intrapatient Variations: First Results from the TESTBREAST Study.

The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities.

Characteristics of tumour stroma in regional lymph node metastases in colorectal cancer patients: a theoretical framework for future diagnostic imaging with FAPI PET/CT.

Purpose: The recently developed fibroblast activation protein inhibitor (FAPI) tracer for PET/CT, binding tumour-stromal cancer-associated fibroblasts, is a promising tool for detection of positive lymph nodes. This study provides an overview of features, including sizes and tumour-stromal content, of lymph nodes and their respective lymph node metastases (LNM) in colorectal cancer (CRC), since literature lacks on whether LNMs contain sufficient stroma to potentially allow FAPI-based tumour detection.

Methods: Haematoxylin and eosin-stained tissue slides from 73 stage III colon cancer patients were included.

Standardization of the tumor-stroma ratio scoring method for breast cancer research.

Purpose: The tumor-stroma ratio (TSR) has repeatedly proven to be correlated with patient outcomes in breast cancer using large retrospective cohorts. However, studies validating the TSR often show variability in methodology, thereby hampering comparisons and uniform outcomes.

Method: This paper provides a detailed description of a simple and uniform TSR scoring method using Hematoxylin and Eosin (H&E)-stained core biopsies and resection tissue, specifically focused on breast cancer.

Serum-based measurements of stromal activation through ADAM12 associate with poor prognosis in colorectal cancer.

Background: Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal activation, A Disintegrin and Metalloprotease 12 (ADAM12) in colorectal cancer (CRC).

Methods: Using gene expression databases we investigated ADAM12 expression in CRC and delineated the source of ADAM12 expression.

RNF12 is regulated by AKT phosphorylation and promotes TGF-β driven breast cancer metastasis.

Transforming growth factor-β (TGF-β) acts as a pro-metastatic factor in advanced breast cancer. RNF12, an E3 ubiquitin ligase, stimulates TGF-β signaling by binding to the inhibitory SMAD7 and inducing its proteasomal degradation. How RNF12 activity is regulated and its exact role in cancer is incompletely understood.

The Stroma Liquid Biopsy Panel Contains a Stromal-Epithelial Gene Signature Ratio That Is Associated with the Histologic Tumor-Stroma Ratio and Predicts Survival in Colon Cancer.

Liquid biopsy has emerged as a novel approach to tumor characterization, offering advantages in sample accessibility and tissue heterogeneity. However, as mutational analysis predominates, the tumor microenvironment has largely remained unacknowledged in liquid biopsy research. The current work provides an explorative transcriptomic characterization of the Stroma Liquid Biopsy (SLB) proteomics panel in colon carcinoma by integrating single-cell and bulk transcriptomics data from publicly available repositories.

Combined Assessment of the Tumor-Stroma Ratio and Tumor Immune Cell Infiltrate for Immune Checkpoint Inhibitor Therapy Response Prediction in Colon Cancer.

The best current biomarker strategies for predicting response to immune checkpoint inhibitor (ICI) therapy fail to account for interpatient variability in response rates. The histologic tumor-stroma ratio (TSR) quantifies intratumoral stromal content and was recently found to be predictive of response to neoadjuvant therapy in multiple cancer types. In the current work, we predicted the likelihood of ICI therapy responsivity of 335 therapy-naive colon adenocarcinoma tumors from The Cancer Genome Atlas, using bioinformatics approaches.

Incidence, timing and risk factors of venous thromboembolic events in patients with pancreatic cancer.

Introduction: Pancreatic cancer is associated with a high risk of venous thromboembolism (VTE). However, comprehensive data on incidence, timing and relevant determinants of VTE in this particular population are scarce. Current study assesses incidence, timing and predictors of VTE in pancreatic cancer through different phases of disease.

Tumour-stroma ratio outperforms tumour budding as biomarker in colon cancer: a cohort study.

The tumour-stroma ratio (TSR) and tumour budding (TB) are two high-risk factors with potential to be implemented in the next TNM classification. The aim of the current study was to evaluate the practical application of the two biomarkers based on reproducibility, independency and prognostic value. Patients diagnosed with stage II or III colon cancer who underwent surgery between 2005 and 2016 were included.

Tumor-stroma ratio is associated with Miller-Payne score and pathological response to neoadjuvant chemotherapy in HER2-negative early breast cancer.

The tumor-stroma ratio (TSR) has proven to be a strong prognostic factor in breast cancer, demonstrating better survival for patients with stroma-low tumors. Since the role of the TSR as a predictive marker for neoadjuvant chemotherapy outcome is yet unknown, this association was evaluated for HER2-negative breast cancer in the prospective DIRECT and NEOZOTAC trials. The TSR was assessed on 375 hematoxylin and eosin-stained sections of pre-treatment biopsies.

Serum N-glycan profiles differ for various breast cancer subtypes.

Breast cancer is the most prevalent cancer in women. Early detection of this disease improves survival and therefore population screenings, based on mammography, are performed. However, the sensitivity of this screening modality is not optimal and new screening methods, such as blood tests, are being explored.

Clinical Perspective on Proteomic and Glycomic Biomarkers for Diagnosis, Prognosis, and Prediction of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival.

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.

Tumour-stroma ratio has poor prognostic value in nonpedunculated T1 colorectal cancer: A multicentre 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.

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.