Journal Article
. 2013 Feb;60(8).
doi: 10.1109/TBME.2013.2245129.

Multi-field-of-view framework for distinguishing tumor grade in ER+ breast cancer from entire histopathology slides

Ajay Basavanhally 1 Shridar Ganesan  Michael Feldman  Natalie Shih  Carolyn Mies  John Tomaszewski  Anant Madabhushi  
Affiliations
  • PMID: 23392336
  •     39 References
  •     29 citations

Abstract

Modified Bloom-Richardson (mBR) grading is known to have prognostic value in breast cancer (BCa), yet its use in clinical practice has been limited by intra- and interobserver variability. The development of a computerized system to distinguish mBR grade from entire estrogen receptor-positive (ER+) BCa histopathology slides will help clinicians identify grading discrepancies and improve overall confidence in the diagnostic result. In this paper, we isolate salient image features characterizing tumor morphology and texture to differentiate entire hematoxylin and eosin (H and E) stained histopathology slides based on mBR grade. The features are used in conjunction with a novel multi-field-of-view (multi-FOV) classifier--a whole-slide classifier that extracts features from a multitude of FOVs of varying sizes--to identify important image features at different FOV sizes. Image features utilized include those related to the spatial arrangement of cancer nuclei (i.e., nuclear architecture) and the textural patterns within nuclei (i.e., nuclear texture). Using slides from 126 ER+ patients (46 low, 60 intermediate, and 20 high mBR grade), our grading system was able to distinguish low versus high, low versus intermediate, and intermediate versus high grade patients with area under curve values of 0.93, 0.72, and 0.74, respectively. Our results suggest that the multi-FOV classifier is able to 1) successfully discriminate low, medium, and high mBR grade and 2) identify specific image features at different FOV sizes that are important for distinguishing mBR grade in H and E stained ER+ BCa histology slides.

Systematic analysis of breast cancer morphology uncovers stromal features associated with survival.
Andrew H Beck, Ankur R Sangoi, +6 authors, Daphne Koller.
Sci Transl Med, 2011 Nov 11; 3(108). PMID: 22072638
Highly Cited.
Computer-assisted assessment of the human epidermal growth factor receptor 2 immunohistochemical assay in imaged histologic sections using a membrane isolation algorithm and quantitative analysis of positive controls.
Bonnie H Hall, Monica Ianosi-Irimie, +3 authors, David J Foran.
BMC Med Imaging, 2008 Jun 07; 8. PMID: 18534031    Free PMC article.
Fractal dimensions of breast lesions on cytology smears.
Pranab Dey, Sambit K Mohanty.
Diagn Cytopathol, 2003 Jul 31; 29(2). PMID: 12889046
A high-throughput active contour scheme for segmentation of histopathological imagery.
Jun Xu, Andrew Janowczyk, Sharat Chandran, Anant Madabhushi.
Med Image Anal, 2011 May 17; 15(6). PMID: 21570336    Free PMC article.
Declining death rates reflect progress against cancer.
Ahmedin Jemal, Elizabeth Ward, Michael Thun.
PLoS One, 2010 Mar 17; 5(3). PMID: 20231893    Free PMC article.
Predicting drug-target interaction networks based on functional groups and biological features.
Zhisong He, Jian Zhang, +4 authors, Kuo-Chen Chou.
PLoS One, 2010 Mar 20; 5(3). PMID: 20300175    Free PMC article.
A multiresolution diffused expectation-maximization algorithm for medical image segmentation.
Giuseppe Boccignone, Paolo Napoletano, Vittorio Caggiano, Mario Ferraro.
Comput Biol Med, 2005 Dec 15; 37(1). PMID: 16352300
Nuclear texture: can it be used as a surrogate endpoint biomarker?
B Palcic.
J Cell Biochem Suppl, 1994 Jan 01; 19. PMID: 7823604
Review.
Histopathologic variables predict Oncotype DX recurrence score.
Melina B Flanagan, David J Dabbs, +2 authors, Rohit Bhargava.
Mod Pathol, 2008 Mar 25; 21(10). PMID: 18360352
Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham histological grades in a series of 825 cases of breast cancer: major importance of the mitotic count as a component of both grading systems.
C Genestie, B Zafrani, +5 authors, X Sastre-Garau.
Anticancer Res, 1998 May 06; 18(1B). PMID: 9568179
Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.
C W Elston, I O Ellis.
Histopathology, 1991 Nov 01; 19(5). PMID: 1757079
Highly Cited.
Feature selection based on mutual information: criteria of max-dependency, max-relevance, and min-redundancy.
Hanchuan Peng, Fuhui Long, Chris Ding.
IEEE Trans Pattern Anal Mach Intell, 2005 Aug 27; 27(8). PMID: 16119262
Highly Cited.
Relationship between tumor grade and computed architectural complexity in breast cancer specimens.
Mauro Tambasco, Anthony M Magliocco.
Hum Pathol, 2008 Apr 29; 39(5). PMID: 18439940
Time-efficient sparse analysis of histopathological whole slide images.
Chao-Hui Huang, Antoine Veillard, +2 authors, Daniel Racoceanu.
Comput Med Imaging Graph, 2010 Dec 15; 35(7-8). PMID: 21145705
Nuclear grading of breast carcinoma by image analysis. Classification by multivariate and neural network analysis.
A E Dawson, R E Austin, D S Weinberg.
Am J Clin Pathol, 1991 Apr 01; 95(4 Suppl 1). PMID: 2008882
Automated breast tumor diagnosis and grading based on wavelet chromatin texture description.
B Weyn, G van de Wouwer, +4 authors, W Jacob.
Cytometry, 1998 Sep 02; 33(1). PMID: 9725556
Automated image morphometry of lobular breast carcinoma.
Logasundaram Rajesh, Pranab Dey, Kusum Joshi.
Anal Quant Cytol Histol, 2002 May 25; 24(2). PMID: 12026054
Cancer statistics, 2012.
Rebecca Siegel, Deepa Naishadham, Ahmedin Jemal.
CA Cancer J Clin, 2012 Jan 13; 62(1). PMID: 22237781
Highly Cited.
Augmented cell-graphs for automated cancer diagnosis.
Cigdem Demir, S Humayun Gultekin, Bülent Yener.
Bioinformatics, 2005 Oct 06; 21 Suppl 2. PMID: 16204128
Multi-field-of-view strategy for image-based outcome prediction of multi-parametric estrogen receptor-positive breast cancer histopathology: Comparison to Oncotype DX.
Ajay Basavanhally, Michael Feldman, +4 authors, Anant Madabhushi.
J Pathol Inform, 2011 Jan 01; 2. PMID: 22811953    Free PMC article.
Breast carcinoma malignancy grading by Bloom-Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index.
John S Meyer, Consuelo Alvarez, +8 authors, Cooperative Breast Cancer Tissue Resource.
Mod Pathol, 2005 May 28; 18(8). PMID: 15920556
Computer-derived nuclear features distinguish malignant from benign breast cytology.
W H Wolberg, W N Street, D M Heisey, O L Mangasarian.
Hum Pathol, 1995 Jul 01; 26(7). PMID: 7628853
Histologic grading of breast cancer: linkage of patient outcome with level of pathologist agreement.
L W Dalton, S E Pinder, +4 authors, R W Blamey.
Mod Pathol, 2000 Jul 27; 13(7). PMID: 10912931
Molecular profiling currently offers no more than tumour morphology and basic immunohistochemistry.
Britta Weigelt, Jorge S Reis-Filho.
Breast Cancer Res, 2011 Jan 05; 12 Suppl 4. PMID: 21172089    Free PMC article.
Computerized image-based detection and grading of lymphocytic infiltration in HER2+ breast cancer histopathology.
Ajay Nagesh Basavanhally, Shridar Ganesan, +5 authors, Anant Madabhushi.
IEEE Trans Biomed Eng, 2009 Nov 04; 57(3). PMID: 19884074
An active learning based classification strategy for the minority class problem: application to histopathology annotation.
Scott Doyle, James Monaco, +2 authors, Anant Madabhushi.
BMC Bioinformatics, 2011 Nov 01; 12. PMID: 22034914    Free PMC article.
Automated detection of regions of interest for tissue microarray experiments: an image texture analysis.
Bilge Karaçali, Aydin Tözeren.
BMC Med Imaging, 2007 Mar 14; 7. PMID: 17349041    Free PMC article.
Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group.
P Boiesen, P O Bendahl, +8 authors, M Fernö.
Acta Oncol, 2001 Feb 07; 39(1). PMID: 10752652
Histopathological image analysis: a review.
Metin N Gurcan, Laura E Boucheron, +3 authors, B Yener.
IEEE Rev Biomed Eng, 2009 Jan 01; 2. PMID: 20671804    Free PMC article.
Highly Cited. Review.
A boosted Bayesian multiresolution classifier for prostate cancer detection from digitized needle biopsies.
Scott Doyle, Michael Feldman, John Tomaszewski, Anant Madabhushi.
IEEE Trans Biomed Eng, 2010 Jun 24; 59(5). PMID: 20570758
Large-scale computations on histology images reveal grade-differentiating parameters for breast cancer.
Sokol Petushi, Fernando U Garcia, +2 authors, Aydin Tozeren.
BMC Med Imaging, 2006 Oct 31; 6. PMID: 17069651    Free PMC article.
Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
Marco Gerlinger, Andrew J Rowan, +28 authors, Charles Swanton.
N Engl J Med, 2012 Mar 09; 366(10). PMID: 22397650    Free PMC article.
Highly Cited.
Minimum redundancy feature selection from microarray gene expression data.
Chris Ding, Hanchuan Peng.
J Bioinform Comput Biol, 2005 Apr 27; 3(2). PMID: 15852500
Highly Cited.
Computer-aided Prognosis of Neuroblastoma on Whole-slide Images: Classification of Stromal Development.
O Sertel, J Kong, +3 authors, M N Gurcan.
Pattern Recognit, 2010 Feb 18; 42(6). PMID: 20161324    Free PMC article.
Fractals in pathology.
S S Cross.
J Pathol, 1997 May 01; 182(1). PMID: 9227334
Review.
Quantification of histochemical staining by color deconvolution.
A C Ruifrok, D A Johnston.
Anal Quant Cytol Histol, 2001 Sep 04; 23(4). PMID: 11531144
Highly Cited.
Morphologic complexity of epithelial architecture for predicting invasive breast cancer survival.
Mauro Tambasco, Misha Eliasziw, Anthony M Magliocco.
J Transl Med, 2011 Jan 05; 8. PMID: 21194459    Free PMC article.
Distance regularized level set evolution and its application to image segmentation.
Chunming Li, Chenyang Xu, Changfeng Gui, Martin D Fox.
IEEE Trans Image Process, 2010 Aug 31; 19(12). PMID: 20801742
Highly Cited.
Detection and classification of thyroid follicular lesions based on nuclear structure from histopathology images.
Wei Wang, John A Ozolek, Gustavo K Rohde.
Cytometry A, 2010 Jan 26; 77(5). PMID: 20099247    Free PMC article.
Computer-based image studies on tumor nests mathematical features of breast cancer and their clinical prognostic value.
Lin-Wei Wang, Ai-Ping Qu, +5 authors, Yan Li.
PLoS One, 2013 Dec 19; 8(12). PMID: 24349253    Free PMC article.
Enhancement of anti-tumor effect of particulate vaccine delivery system by 'bacteriomimetic' CpG functionalization of poly-lactic-co-glycolic acid nanoparticles.
Rutika A Kokate, Sanjay I Thamake, +4 authors, Harlan P Jones.
Nanomedicine (Lond), 2015 Apr 14; 10(6). PMID: 25867857    Free PMC article.
Predicting classifier performance with limited training data: applications to computer-aided diagnosis in breast and prostate cancer.
Ajay Basavanhally, Satish Viswanath, Anant Madabhushi.
PLoS One, 2015 May 21; 10(5). PMID: 25993029    Free PMC article.
New breast cancer prognostic factors identified by computer-aided image analysis of HE stained histopathology images.
Jia-Mei Chen, Ai-Ping Qu, +7 authors, Yan Li.
Sci Rep, 2015 May 30; 5. PMID: 26022540    Free PMC article.
Localization of Diagnostically Relevant Regions of Interest in Whole Slide Images: a Comparative Study.
Ezgi Mercan, Selim Aksoy, +3 authors, Joann G Elmore.
J Digit Imaging, 2016 Mar 11; 29(4). PMID: 26961982    Free PMC article.
Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.
Rohit Bhargava, Anant Madabhushi.
Annu Rev Biomed Eng, 2016 Jul 16; 18. PMID: 27420575    Free PMC article.
Review.
Image analysis and machine learning in digital pathology: Challenges and opportunities.
Anant Madabhushi, George Lee.
Med Image Anal, 2016 Jul 18; 33. PMID: 27423409    Free PMC article.
Highly Cited. Review.
Multi-Pass Adaptive Voting for Nuclei Detection in Histopathological Images.
Cheng Lu, Hongming Xu, +3 authors, Anant Madabhushi.
Sci Rep, 2016 Oct 04; 6. PMID: 27694950    Free PMC article.
Evaluating stability of histomorphometric features across scanner and staining variations: prostate cancer diagnosis from whole slide images.
Patrick Leo, George Lee, +3 authors, Anant Madabhushi.
J Med Imaging (Bellingham), 2016 Nov 03; 3(4). PMID: 27803941    Free PMC article.
Computer-based image analysis in breast pathology.
Ziba Gandomkar, Patrick C Brennan, Claudia Mello-Thoms.
J Pathol Inform, 2017 Jan 10; 7. PMID: 28066683    Free PMC article.
Review.
Accurate and reproducible invasive breast cancer detection in whole-slide images: A Deep Learning approach for quantifying tumor extent.
Angel Cruz-Roa, Hannah Gilmore, +6 authors, Anant Madabhushi.
Sci Rep, 2017 Apr 19; 7. PMID: 28418027    Free PMC article.
Highly Cited.
An oral cavity squamous cell carcinoma quantitative histomorphometric-based image classifier of nuclear morphology can risk stratify patients for disease-specific survival.
Cheng Lu, James S Lewis, +3 authors, Anant Madabhushi.
Mod Pathol, 2017 Aug 05; 30(12). PMID: 28776575    Free PMC article.
Multi-Instance Multi-Label Learning for Multi-Class Classification of Whole Slide Breast Histopathology Images.
Caner Mercan, Selim Aksoy, +3 authors, Joann G Elmore.
IEEE Trans Med Imaging, 2017 Oct 06; 37(1). PMID: 28981408    Free PMC article.
An improved deep learning approach for detection of thyroid papillary cancer in ultrasound images.
Hailiang Li, Jian Weng, +5 authors, Jiajie Zhang.
Sci Rep, 2018 Apr 28; 8(1). PMID: 29700427    Free PMC article.
High-throughput adaptive sampling for whole-slide histopathology image analysis (HASHI) via convolutional neural networks: Application to invasive breast cancer detection.
Angel Cruz-Roa, Hannah Gilmore, +6 authors, Fabio González.
PLoS One, 2018 May 26; 13(5). PMID: 29795581    Free PMC article.
Quantitative nuclear histomorphometry predicts oncotype DX risk categories for early stage ER+ breast cancer.
Jon Whitney, German Corredor, +6 authors, Anant Madabhushi.
BMC Cancer, 2018 Jun 01; 18(1). PMID: 29848291    Free PMC article.
Nuclear shape and orientation features from H&E images predict survival in early-stage estrogen receptor-positive breast cancers.
Cheng Lu, David Romo-Bucheli, +5 authors, Anant Madabhushi.
Lab Invest, 2018 Jul 01; 98(11). PMID: 29959421    Free PMC article.
Stable and discriminating features are predictive of cancer presence and Gleason grade in radical prostatectomy specimens: a multi-site study.
Patrick Leo, Robin Elliott, +3 authors, Anant Madabhushi.
Sci Rep, 2018 Oct 10; 8(1). PMID: 30297720    Free PMC article.
Artificial intelligence in digital pathology - new tools for diagnosis and precision oncology.
Kaustav Bera, Kurt A Schalper, +2 authors, Anant Madabhushi.
Nat Rev Clin Oncol, 2019 Aug 11; 16(11). PMID: 31399699    Free PMC article.
Highly Cited. Review.
MLCD: A Unified Software Package for Cancer Diagnosis.
Wenjun Wu, Beibin Li, +5 authors, Linda G Shapiro.
JCO Clin Cancer Inform, 2020 Mar 29; 4. PMID: 32216637    Free PMC article.
Efficient Deep Learning Architecture for Detection and Recognition of Thyroid Nodules.
Jingzhe Ma, Shaobo Duan, +6 authors, Huimin Ma.
Comput Intell Neurosci, 2020 Aug 25; 2020. PMID: 32831817    Free PMC article.
Piloting a Deep Learning Model for Predicting Nuclear BAP1 Immunohistochemical Expression of Uveal Melanoma from Hematoxylin-and-Eosin Sections.
Hongrun Zhang, Helen Kalirai, +3 authors, Sarah E Coupland.
Transl Vis Sci Technol, 2020 Sep 22; 9(2). PMID: 32953248    Free PMC article.
Detection and classification of cancer in whole slide breast histopathology images using deep convolutional networks.
Baris Gecer, Selim Aksoy, +3 authors, Joann G Elmore.
Pattern Recognit, 2019 Jan 27; 84. PMID: 30679879    Free PMC article.
Convolutional neural network initialized active contour model with adaptive ellipse fitting for nuclear segmentation on breast histopathological images.
Jun Xu, Lei Gong, +4 authors, Anant Madabhushi.
J Med Imaging (Bellingham), 2019 Mar 07; 6(1). PMID: 30840729    Free PMC article.
Generating Region of Interests for Invasive Breast Cancer in Histopathological Whole-Slide-Image.
Shreyas Malakarjun Patil, Li Tong, May D Wang.
Proc COMPSAC, 2020 Oct 09; 2020. PMID: 33029594    Free PMC article.
Computer-Aided Histopathological Image Analysis Techniques for Automated Nuclear Atypia Scoring of Breast Cancer: a Review.
Asha Das, Madhu S Nair, S David Peter.
J Digit Imaging, 2020 Jan 29; 33(5). PMID: 31989390    Free PMC article.
Review.
Evaluating reproducibility of AI algorithms in digital pathology with DAPPER.
Andrea Bizzego, Nicole Bussola, +6 authors, Cesare Furlanello.
PLoS Comput Biol, 2019 Mar 28; 15(3). PMID: 30917113    Free PMC article.
Image Descriptors for Weakly Annotated Histopathological Breast Cancer Data.
Panagiotis Stanitsas, Anoop Cherian, +3 authors, Alexander Truskinovsky.
Front Digit Health, 2020 Dec 22; 2. PMID: 33345255    Free PMC article.
Artificial intelligence in automatic classification of invasive ductal carcinoma breast cancer in digital pathology images.
Mohammad Abdolahi, Mohammad Salehi, Iman Shokatian, Reza Reiazi.
Med J Islam Repub Iran, 2021 Jan 14; 34. PMID: 33437736    Free PMC article.