83 research outputs found
ACROBAT -- a multi-stain breast cancer histological whole-slide-image data set from routine diagnostics for computational pathology
The analysis of FFPE tissue sections stained with haematoxylin and eosin
(H&E) or immunohistochemistry (IHC) is an essential part of the pathologic
assessment of surgically resected breast cancer specimens. IHC staining has
been broadly adopted into diagnostic guidelines and routine workflows to
manually assess status and scoring of several established biomarkers, including
ER, PGR, HER2 and KI67. However, this is a task that can also be facilitated by
computational pathology image analysis methods. The research in computational
pathology has recently made numerous substantial advances, often based on
publicly available whole slide image (WSI) data sets. However, the field is
still considerably limited by the sparsity of public data sets. In particular,
there are no large, high quality publicly available data sets with WSIs of
matching IHC and H&E-stained tissue sections. Here, we publish the currently
largest publicly available data set of WSIs of tissue sections from surgical
resection specimens from female primary breast cancer patients with matched
WSIs of corresponding H&E and IHC-stained tissue, consisting of 4,212 WSIs from
1,153 patients. The primary purpose of the data set was to facilitate the
ACROBAT WSI registration challenge, aiming at accurately aligning H&E and IHC
images. For research in the area of image registration, automatic quantitative
feedback on registration algorithm performance remains available through the
ACROBAT challenge website, based on more than 37,000 manually annotated
landmark pairs from 13 annotators. Beyond registration, this data set has the
potential to enable many different avenues of computational pathology research,
including stain-guided learning, virtual staining, unsupervised pre-training,
artefact detection and stain-independent models
Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration
Aims The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections. Methods and results Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot-spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method [confidence interval (CI) = 0.87; 95% CI = 0.799-0.93] marginally met the prespecified success criterion (lower 95% CI >= 0.8), while the ICC for the hot-spot method (0.83; 95% CI = 0.74-0.90) did not. Visually, interobserver concordance in location of selected hot-spots varies between cases. The median times for scoring were 9 and 6 min for global and hot-spot methods, respectively. Conclusions The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further
The ACROBAT 2022 Challenge: Automatic Registration Of Breast Cancer Tissue
The alignment of tissue between histopathological whole-slide-images (WSI) is
crucial for research and clinical applications. Advances in computing, deep
learning, and availability of large WSI datasets have revolutionised WSI
analysis. Therefore, the current state-of-the-art in WSI registration is
unclear. To address this, we conducted the ACROBAT challenge, based on the
largest WSI registration dataset to date, including 4,212 WSIs from 1,152
breast cancer patients. The challenge objective was to align WSIs of tissue
that was stained with routine diagnostic immunohistochemistry to its
H&E-stained counterpart. We compare the performance of eight WSI registration
algorithms, including an investigation of the impact of different WSI
properties and clinical covariates. We find that conceptually distinct WSI
registration methods can lead to highly accurate registration performances and
identify covariates that impact performances across methods. These results
establish the current state-of-the-art in WSI registration and guide
researchers in selecting and developing methods
Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.Peer reviewe
Pitfalls in machine learningâbased assessment of tumorâinfiltrating lymphocytes in breast cancer: a report of the international immunoâoncology biomarker working group
The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC
Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.
Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (Pâ<â5.0âĂâ10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rateâ<â0.05). Five loci showed associations (Pâ<â0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores
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Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls
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