Dataset Information

Digital Assessment of Stained Breast Tissue Images for Comprehensive Tumor and Microenvironment Analysis.

ABSTRACT: Current histopathological diagnosis involves human expert interpretation of stained images for diagnosis. This process is prone to inter-observer variability, often leading to low concordance rates amongst pathologists across many types of tissues. Further, since structural features are mostly just defined for epithelial alterations during tumor progression, the use of associated stromal changes is limited. Here we sought to examine whether digital analysis of commonly used hematoxylin and eosin-stained images could provide precise and quantitative metrics of disease from both epithelial and stromal cells. We developed a convolutional neural network approach to identify epithelial breast cells from their microenvironment. Second, we analyzed the microenvironment to further observe different constituent cells using unsupervised clustering. Finally, we categorized breast cancer by the combined effects of stromal and epithelial inertia. Together, the work provides insight and evidence of cancer association for interpretable features from deep learning methods that provide new opportunities for comprehensive analysis of standard pathology images.

SUBMITTER: Mittal S

PROVIDER: S-EPMC6797859 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Digital Assessment of Stained Breast Tissue Images for Comprehensive Tumor and Microenvironment Analysis.

Mittal Shachi S Stoean Catalin C Kajdacsy-Balla Andre A Bhargava Rohit R

Frontiers in bioengineering and biotechnology 20191001

Current histopathological diagnosis involves human expert interpretation of stained images for diagnosis. This process is prone to inter-observer variability, often leading to low concordance rates amongst pathologists across many types of tissues. Further, since structural features are mostly just defined for epithelial alterations during tumor progression, the use of associated stromal changes is limited. Here we sought to examine whether digital analysis of commonly used hematoxylin and eosin ...[more]

PMID: 31681737

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Project description:Purpose:The proliferation marker Ki-67 has been used as a prognostic marker to separate low- and high-risk breast cancer subtypes and guide treatment decisions for adjuvant chemotherapy. The association of Ki-67 with response to tamoxifen therapy is unclear. High-throughput automated scoring of Ki-67 might enable standardization of quantification and definition of clinical cut-off values. We hypothesized that digital image analysis (DIA) of Ki-67 can be used to evaluate proliferation in breast cancer tumors, and that Ki-67 may be associated with tamoxifen resistance in early-stage breast cancer. Patients and Methods:Here, we apply DIA technology from Visiopharm using a custom designed algorithm for quantifying the expression of Ki-67, in a case-control study nested in the Danish Breast Cancer Group clinical database, consisting of stages I, II, or III breast cancer patients of 35-69 years of age, diagnosed during 1985-2001, in the Jutland peninsula, Denmark. We assessed DIA-Ki-67 score on tissue microarrays (TMAs) from breast cancer patients in a case-control study including 541 ER-positive and 300 ER-negative recurrent cases and their non-recurrent controls, matched on ER-status, cancer stage, menopausal status, year of diagnosis, and county of residence. We used logistic regression to estimate odds ratios and associated 95% confidence intervals to determine the association of Ki-67 expression with recurrence risk, adjusting for matching factors, chemotherapy, type of surgery, receipt of radiation therapy, age category, and comorbidity. Results:Ki-67 was not associated with increased risk of recurrence in tamoxifen-treated patients (ORadj =0.72, 95% CI 0.54, 0.96) or ER-negative patients (ORadj =0.85, 95% CI 0.54, 1.34). Conclusion:Our findings suggest that Ki-67 digital image analysis in TMAs is not associated with increased risk of recurrence among tamoxifen-treated ER-positive breast cancer or ER-negative breast cancer patients. Overall, our findings do not support an increased risk of recurrence associated with Ki-67 expression.

Project description:BackgroundCuproptosis is a newly discovered programmed cell death dependent on overload copper-induced mitochondrial respiration dysregulation. The positive response to immunotherapy, one of the most important treatments for invasive breast cancer, depends on the dynamic balance between tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). However, cuproptosis-related genes (CRGs) in clinical prognosis, immune cell infiltration, and immunotherapy response remain unclear in breast cancer progression.MethodsThe expression and mutation patterns of 12 cuproptosis-related genes were systematically evaluated in the BRCA training group. Through unsupervised clustering analysis and developing a cuproptosis-related scoring system, we further explored the relationship between cuproptosis and breast cancer progression, prognosis, immune cell infiltration, and immunotherapy.ResultsWe identified two distinct CuproptosisClusters, which were correlated with the different patterns between clinicopathological features, prognosis, and immune cell infiltration. Moreover, the differences of the three cuproptosis-related gene subtypes were evaluated based on the CuproptosisCluster-related DEGs. Then, a cuproptosis-related gene signature (PGK1, SLC52A2, SEC14L2, RAD23B, SLC16A6, CCL5, and MAL2) and the scoring system were constructed to quantify the cuproptosis pattern of BRCA patients in the training cohort, and the testing cohorts validated them. Specifically, patients from the low-CRG_score group were characterized by higher immune cell infiltration, immune checkpoint expression, immune checkpoint inhibitor (ICI) scores, and greater sensitivity to immunotherapy. Finally, we screened out RAD23B as a favorable target and indicated its expression was associated with breast cancer progression, drug resistance, and poor prognosis in BRCA patients by performing real-time RT-PCR, cell viability, and IC50 assay.ConclusionsOur results confirmed the essential function of cuproptosis in regulating the progression, prognosis, immune cell infiltration, and response to breast cancer immunotherapy. Quantifying cuproptosis patterns and constructing a CRG_score could help explore the potential molecular mechanisms of cuproptosis regulating BRCA advancement and provide more effective immunotherapy and chemotherapy targets.

Dataset Information

Digital Assessment of Stained Breast Tissue Images for Comprehensive Tumor and Microenvironment Analysis.

Publications

Digital Assessment of Stained Breast Tissue Images for Comprehensive Tumor and Microenvironment Analysis.

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