Journal Article
. 2008 Oct; 10(5):R89.
doi: 10.1186/bcr2187.

Novel image analysis approach for quantifying expression of nuclear proteins assessed by immunohistochemistry: application to measurement of oestrogen and progesterone receptor levels in breast cancer

Elton Rexhepaj 1 Donal J Brennan  Peter Holloway  Elaine W Kay  Amanda H McCann  Goran Landberg  Michael J Duffy  Karin Jirstrom  William M Gallagher  
Affiliations
  • PMID: 18947395
  •     33 References
  •     55 citations

Abstract

Introduction: Manual interpretation of immunohistochemistry (IHC) is a subjective, time-consuming and variable process, with an inherent intra-observer and inter-observer variability. Automated image analysis approaches offer the possibility of developing rapid, uniform indicators of IHC staining. In the present article we describe the development of a novel approach for automatically quantifying oestrogen receptor (ER) and progesterone receptor (PR) protein expression assessed by IHC in primary breast cancer.

Methods: Two cohorts of breast cancer patients (n = 743) were used in the study. Digital images of breast cancer tissue microarrays were captured using the Aperio ScanScope XT slide scanner (Aperio Technologies, Vista, CA, USA). Image analysis algorithms were developed using MatLab 7 (MathWorks, Apple Hill Drive, MA, USA). A fully automated nuclear algorithm was developed to discriminate tumour from normal tissue and to quantify ER and PR expression in both cohorts. Random forest clustering was employed to identify optimum thresholds for survival analysis.

Results: The accuracy of the nuclear algorithm was initially confirmed by a histopathologist, who validated the output in 18 representative images. In these 18 samples, an excellent correlation was evident between the results obtained by manual and automated analysis (Spearman's rho = 0.9, P < 0.001). Optimum thresholds for survival analysis were identified using random forest clustering. This revealed 7% positive tumour cells as the optimum threshold for the ER and 5% positive tumour cells for the PR. Moreover, a 7% cutoff level for the ER predicted a better response to tamoxifen than the currently used 10% threshold. Finally, linear regression was employed to demonstrate a more homogeneous pattern of expression for the ER (R = 0.860) than for the PR (R = 0.681).

Conclusions: In summary, we present data on the automated quantification of the ER and the PR in 743 primary breast tumours using a novel unsupervised image analysis algorithm. This novel approach provides a useful tool for the quantification of biomarkers on tissue specimens, as well as for objective identification of appropriate cutoff thresholds for biomarker positivity. It also offers the potential to identify proteins with a homogeneous pattern of expression.

Assessment of interlaboratory variation in the immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray.
Robin L Parker, David G Huntsman, +4 authors, C Blake Gilks.
Am J Clin Pathol, 2002 Jul 02; 117(5). PMID: 12090420
Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5,993 breast cancers.
Mehrdad Nadji, Carmen Gomez-Fernandez, Parvin Ganjei-Azar, Azorides R Morales.
Am J Clin Pathol, 2005 Mar 15; 123(1). PMID: 15762276
Automated subcellular localization and quantification of protein expression in tissue microarrays.
Robert L Camp, Gina G Chung, David L Rimm.
Nat Med, 2002 Oct 22; 8(11). PMID: 12389040
Highly Cited.
Adjuvant hormonal therapy for premenopausal women with breast cancer.
Leisha A Emens, Nancy E Davidson.
Clin Cancer Res, 2003 Jan 23; 9(1 Pt 2). PMID: 12538505
Adjuvant endocrine therapy.
Lars E Rutqvist.
Best Pract Res Clin Endocrinol Metab, 2003 Dec 23; 18(1). PMID: 14687599
Review.
Interobserver agreement for estrogen receptor immunohistochemical analysis in breast cancer: a comparison of manual and computer-assisted scoring methods.
Leslie K Diaz, Aysegul Sahin, Nour Sneige.
Ann Diagn Pathol, 2004 May 08; 8(1). PMID: 15129906
Immunohistochemical evaluation of hormone receptors in breast cancer: which scoring system is suitable for highly sensitive procedures?
Shinobu Umemura, Johbu Itoh, +6 authors, R Yoshiyuki Osamura.
Appl Immunohistochem Mol Morphol, 2004 May 28; 12(1). PMID: 15163012
Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study.
Lisa A Carey, Charles M Perou, +14 authors, Robert C Millikan.
JAMA, 2006 Jun 08; 295(21). PMID: 16757721
Highly Cited.
Novel prognostic immunohistochemical biomarker panel for estrogen receptor-positive breast cancer.
Brian Z Ring, Robert S Seitz, +9 authors, Douglas T Ross.
J Clin Oncol, 2006 Jul 01; 24(19). PMID: 16809728
Tumor classification by tissue microarray profiling: random forest clustering applied to renal cell carcinoma.
Tao Shi, David Seligson, +2 authors, Steve Horvath.
Mod Pathol, 2004 Nov 06; 18(4). PMID: 15529185
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Lancet, 2005 May 17; 365(9472). PMID: 15894097
Highly Cited.
Global histone modification patterns predict risk of prostate cancer recurrence.
David B Seligson, Steve Horvath, +4 authors, Siavash K Kurdistani.
Nature, 2005 Jul 01; 435(7046). PMID: 15988529
Highly Cited.
Tissue microarrays: bridging the gap between research and the clinic.
Till Braunschweig, Joon-Yong Chung, Stephen M Hewitt.
Expert Rev Proteomics, 2005 Jul 08; 2(3). PMID: 16000080
Review.
Application of DNA microarray technology in determining breast cancer prognosis and therapeutic response.
Donal J Brennan, Sallyann L O'Brien, +4 authors, William M Gallagher.
Expert Opin Biol Ther, 2005 Jul 30; 5(8). PMID: 16050784
Review.
Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005.
A Goldhirsch, J H Glick, +4 authors, Panel members.
Ann Oncol, 2005 Sep 09; 16(10). PMID: 16148022
Highly Cited.
A human protein atlas for normal and cancer tissues based on antibody proteomics.
Mathias Uhlén, Erik Björling, +64 authors, Fredrik Pontén.
Mol Cell Proteomics, 2005 Aug 30; 4(12). PMID: 16127175
Highly Cited.
Automated quantitative analysis (AQUA) of in situ protein expression, antibody concentration, and prognosis.
Anthony McCabe, Marisa Dolled-Filhart, Robert L Camp, David L Rimm.
J Natl Cancer Inst, 2005 Dec 22; 97(24). PMID: 16368942
A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.
Breast International Group (BIG) 1-98 Collaborative Group, Beat Thürlimann, +13 authors, Aron Goldhirsch.
N Engl J Med, 2005 Dec 31; 353(26). PMID: 16382061
Highly Cited.
Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment I.
R A Walker.
Histopathology, 2006 Sep 19; 49(4). PMID: 16978204
Review.
Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment II.
C R Taylor, R M Levenson.
Histopathology, 2006 Sep 19; 49(4). PMID: 16978205
Highly Cited. Review.
CA IX is an independent prognostic marker in premenopausal breast cancer patients with one to three positive lymph nodes and a putative marker of radiation resistance.
Donal J Brennan, Karin Jirstrom, +6 authors, Sallyann L O'Brien.
Clin Cancer Res, 2006 Nov 07; 12(21). PMID: 17085655
New perspectives into the biological and clinical relevance of oestrogen receptors in the human breast.
V Speirs, R A Walker.
J Pathol, 2007 Jan 20; 211(5). PMID: 17236182
Review.
Quantitative analysis of estrogen receptor heterogeneity in breast cancer.
Gina G Chung, Maciej P Zerkowski, +2 authors, David L Rimm.
Lab Invest, 2007 Mar 06; 87(7). PMID: 17334408
Contribution of DNA and tissue microarray technology to the identification and validation of biomarkers and personalised medicine in breast cancer.
Donal J Brennan, Catherine Kelly, +3 authors, William M Gallagher.
Cancer Genomics Proteomics, 2007 Sep 20; 4(3). PMID: 17878516
Review.
Assessment of two automated imaging systems in evaluating estrogen receptor status in breast carcinoma.
Sumita Gokhale, Daniel Rosen, +5 authors, Constance T Albarracin.
Appl Immunohistochem Mol Morphol, 2007 Dec 20; 15(4). PMID: 18091390
Can clinically relevant prognostic subsets of breast cancer patients with four or more involved axillary lymph nodes be identified through immunohistochemical biomarkers? A tissue microarray feasibility study.
Simon J Crabb, Chris D Bajdik, +4 authors, Karen A Gelmon.
Breast Cancer Res, 2008 Jan 16; 10(1). PMID: 18194560    Free PMC article.
Prognostic ability of a panel of immunohistochemistry markers - retailoring of an 'old solution'.
Donal J Brennan, William M Gallagher.
Breast Cancer Res, 2008 Mar 12; 10(1). PMID: 18331621    Free PMC article.
Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer.
Donal J Brennan, Elton Rexhepaj, +11 authors, William M Gallagher.
Clin Cancer Res, 2008 May 03; 14(9). PMID: 18451232    Free PMC article.
Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring: a tissue microarray study of 3,484 cases.
Dmitry A Turbin, Samuel Leung, +12 authors, David G Huntsman.
Breast Cancer Res Treat, 2007 Oct 04; 110(3). PMID: 17912629
Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma.
Torsten O Nielsen, Forrest D Hsu, +13 authors, Charles M Perou.
Clin Cancer Res, 2004 Aug 26; 10(16). PMID: 15328174
Highly Cited.
Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer.
A Howell, J Cuzick, +8 authors, ATAC Trialists' Group.
Lancet, 2005 Jan 11; 365(9453). PMID: 15639680
Highly Cited.
Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up.
Lisa Rydén, Per-Ebbe Jönsson, +10 authors, South-East Swedish Breast Cancer Group.
Eur J Cancer, 2005 Jan 22; 41(2). PMID: 15661551
Quality assurance in immunohistochemistry: results of an interlaboratory trial involving 172 pathologists.
Thomas Rüdiger, H Höfler, +8 authors, H K Müller-Hermelink.
Am J Surg Pathol, 2002 Jul 20; 26(7). PMID: 12131154
Image analysis algorithms for immunohistochemical assessment of cell death events and fibrosis in tissue sections.
Maryla Krajewska, Layton H Smith, +8 authors, Stan Krajewski.
J Histochem Cytochem, 2009 Mar 18; 57(7). PMID: 19289554    Free PMC article.
High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer.
A Gaber, M Johansson, +6 authors, H Birgisson.
Br J Cancer, 2009 Apr 23; 100(10). PMID: 19384300    Free PMC article.
A genetic programming approach for Burkholderia pseudomallei diagnostic pattern discovery.
Zheng Rong Yang, Ganjana Lertmemongkolchai, +2 authors, Richard Titball.
Bioinformatics, 2009 Jun 30; 25(17). PMID: 19561021    Free PMC article.
Protein modifications as potential biomarkers in breast cancer.
Hongjun Jin, Richard C Zangar.
Biomark Insights, 2010 Jan 15; 4. PMID: 20072669    Free PMC article.
Assessment of automated image analysis of breast cancer tissue microarrays for epidemiologic studies.
Kelly L Bolton, Montserrat Garcia-Closas, +12 authors, Mark E Sherman.
Cancer Epidemiol Biomarkers Prev, 2010 Mar 25; 19(4). PMID: 20332278    Free PMC article.
Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.
Donal J Brennan, Jenny Brändstedt, +7 authors, Karin Jirstrom.
BMC Cancer, 2010 Apr 03; 10. PMID: 20359358    Free PMC article.
Image analysis as an adjunct to manual HER-2 immunohistochemical review: a diagnostic tool to standardize interpretation.
Lynne Dobson, Catherine Conway, +8 authors, Elaine Kay.
Histopathology, 2010 Jun 30; 57(1). PMID: 20584089    Free PMC article.
ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67.
Vilppu J Tuominen, Sanna Ruotoistenmäki, +2 authors, Jorma Isola.
Breast Cancer Res, 2010 Jul 29; 12(4). PMID: 20663194    Free PMC article.
Highly Cited.
Antibody-based proteomics: fast-tracking molecular diagnostics in oncology.
Donal J Brennan, Darran P O'Connor, +2 authors, William M Gallagher.
Nat Rev Cancer, 2010 Aug 20; 10(9). PMID: 20720569
Review.
TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.
G M Marshall, J L Bell, +12 authors, B B Cheung.
Oncogene, 2010 Aug 24; 29(46). PMID: 20729920    Free PMC article.
VEGFR-2 expression in tumor tissue of breast cancer patients.
A A Lushnikova, I B Nasunova, +2 authors, E B Kampova-Polevaya.
Dokl Biol Sci, 2010 Oct 22; 434. PMID: 20963665
Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer.
Elton Rexhepaj, Karin Jirstrom, +5 authors, William M Gallagher.
BMC Cancer, 2010 Nov 26; 10. PMID: 21092276    Free PMC article.
Stromal expression of β-arrestin-1 predicts clinical outcome and tamoxifen response in breast cancer.
Katja Lundgren, Nicholas P Tobin, +4 authors, Göran Landberg.
J Mol Diagn, 2011 Apr 19; 13(3). PMID: 21497294    Free PMC article.
Image analysis tools for evaluation of microscopic views of immunohistochemically stained specimen in medical research-a review.
Keerthana Prasad, Gopalakrishna K Prabhu.
J Med Syst, 2011 May 18; 36(4). PMID: 21584771
Review.
Quantitative image analysis in the assessment of diffuse large B-cell lymphoma.
Devon S Chabot-Richards, David R Martin, +2 authors, Kristin E Hunt.
Mod Pathol, 2011 Aug 16; 24(12). PMID: 21841768    Free PMC article.
The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation.
Sandra Sernbo, Elin Gustavsson, +6 authors, Sara Ek.
BMC Cancer, 2011 Sep 29; 11. PMID: 21943380    Free PMC article.
Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy.
David G DeNardo, Donal J Brennan, +12 authors, Lisa M Coussens.
Cancer Discov, 2011 Nov 01; 1(1). PMID: 22039576    Free PMC article.
Highly Cited.
Identification of prognostic biomarkers for glioblastomas using protein expression profiling.
Yong Jung, Kyeung Min Joo, +12 authors, Do-Hyun Nam.
Int J Oncol, 2011 Dec 20; 40(4). PMID: 22179774    Free PMC article.
Identification of tumor epithelium and stroma in tissue microarrays using texture analysis.
Nina Linder, Juho Konsti, +7 authors, Johan Lundin.
Diagn Pathol, 2012 Mar 06; 7. PMID: 22385523    Free PMC article.
Development of multigene expression signature maps at the protein level from digitized immunohistochemistry slides.
Gregory J Metzger, Stephen C Dankbar, +3 authors, Stephen C Schmechel.
PLoS One, 2012 Mar 23; 7(3). PMID: 22438942    Free PMC article.
Comparison of evaluations of hormone receptors in breast carcinoma by image-analysis using three automated immunohistochemical stainings.
Koji Arihiro, Miyo Oda, +9 authors, Maiko Tanaka.
Exp Ther Med, 2010 Nov 01; 1(6). PMID: 22993620    Free PMC article.
Low ERK phosphorylation in cancer-associated fibroblasts is associated with tamoxifen resistance in pre-menopausal breast cancer.
Susann Busch, Lisa Rydén, +2 authors, Göran Landberg.
PLoS One, 2012 Oct 03; 7(9). PMID: 23029174    Free PMC article.
Molecular portrait-based correlation between primary canine mammary tumor and its lymph node metastasis: possible prognostic-predictive models and/or stronghold for specific treatments?
Germana Beha, Barbara Brunetti, +5 authors, Cinzia Benazzi.
BMC Vet Res, 2012 Nov 14; 8. PMID: 23146872    Free PMC article.
Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses.
Jonathan B Mitchem, Donal J Brennan, +16 authors, David G DeNardo.
Cancer Res, 2012 Dec 12; 73(3). PMID: 23221383    Free PMC article.
Highly Cited.
Astronomical algorithms for automated analysis of tissue protein expression in breast cancer.
H R Ali, M Irwin, +8 authors, C Caldas.
Br J Cancer, 2013 Jan 19; 108(3). PMID: 23329232    Free PMC article.
A texture based pattern recognition approach to distinguish melanoma from non-melanoma cells in histopathological tissue microarray sections.
Elton Rexhepaj, Margrét Agnarsdóttir, +6 authors, Fredrik Ponten.
PLoS One, 2013 May 22; 8(5). PMID: 23690928    Free PMC article.
Automated classification of immunostaining patterns in breast tissue from the human protein atlas.
Issac Niwas Swamidoss, Andreas Kårsnäs, +5 authors, Robin Strand.
J Pathol Inform, 2013 Jun 15; 4(Suppl). PMID: 23766936    Free PMC article.
Construction and analysis of multiparameter prognostic models for melanoma outcome.
Bonnie E Gould Rothberg, David L Rimm.
Methods Mol Biol, 2013 Nov 22; 1102. PMID: 24258982    Free PMC article.
Systematic Review.
Phosphorylated p-70S6K predicts tamoxifen resistance in postmenopausal breast cancer patients randomized between adjuvant tamoxifen versus no systemic treatment.
Karin Beelen, Mark Opdam, +8 authors, Sabine C Linn.
Breast Cancer Res, 2014 Jan 23; 16(1). PMID: 24447434    Free PMC article.
Decreased expression of Yes-associated protein is associated with outcome in the luminal A breast cancer subgroup and with an impaired tamoxifen response.
Sophie Lehn, Nicholas P Tobin, +4 authors, Göran Landberg.
BMC Cancer, 2014 Feb 25; 14. PMID: 24559095    Free PMC article.
IHC Profiler: an open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples.
Frency Varghese, Amirali B Bukhari, Renu Malhotra, Abhijit De.
PLoS One, 2014 May 08; 9(5). PMID: 24802416    Free PMC article.
Highly Cited.
Novel nuclear localization of fatty acid synthase correlates with prostate cancer aggressiveness.
Allison A Madigan, Kevin J Rycyna, +7 authors, Denise S O'Keefe.
Am J Pathol, 2014 Jun 08; 184(8). PMID: 24907642    Free PMC article.
Reliable quantification of protein expression and cellular localization in histological sections.
Michaela Schlederer, Kristina M Mueller, +7 authors, Lukas Kenner.
PLoS One, 2014 Jul 12; 9(7). PMID: 25013898    Free PMC article.
Image segmentation and identification of paired antibodies in breast tissue.
Jimmy C Azar, Martin Simonsson, Ewert Bengtsson, Anders Hast.
Comput Math Methods Med, 2014 Jul 26; 2014. PMID: 25061472    Free PMC article.
Circadian rhythm reprogramming during lung inflammation.
Jeffrey A Haspel, Sukrutha Chettimada, +13 authors, Augustine M K Choi.
Nat Commun, 2014 Sep 12; 5. PMID: 25208554    Free PMC article.
Development of a computational high-throughput tool for the quantitative examination of dose-dependent histological features.
Rance Nault, Dirk Colbry, +2 authors, Timothy R Zacharewski.
Toxicol Pathol, 2014 Oct 03; 43(3). PMID: 25274660    Free PMC article.
Effects of tissue decalcification on the quantification of breast cancer biomarkers by digital image analysis.
Arkadiusz Gertych, Sonia Mohan, +5 authors, Beatrice S Knudsen.
Diagn Pathol, 2014 Nov 26; 9. PMID: 25421113    Free PMC article.
Progesterone metabolites regulate induction, growth, and suppression of estrogen- and progesterone receptor-negative human breast cell tumors.
John P Wiebe, Guihua Zhang, Ian Welch, Heather-Anne T Cadieux-Pitre.
Breast Cancer Res, 2013 Jan 01; 15(3). PMID: 25927181    Free PMC article.
Using Pharmacokinetic Profiles and Digital Quantification of Stained Tissue Microarrays as a Medium-Throughput, Quantitative Method for Measuring the Kinetics of Early Signaling Changes Following Integrin-Linked Kinase Inhibition in an In Vivo Model of Cancer.
Jessica Kalra, Weislawa H Dragowska, Marcel B Bally.
J Histochem Cytochem, 2015 May 06; 63(9). PMID: 25940338    Free PMC article.
Decrease of miR-146a is associated with the aggressiveness of human oral squamous cell carcinoma.
Zonggao Shi, Jeffrey J Johnson, +2 authors, M Sharon Stack.
Arch Oral Biol, 2015 Jul 15; 60(9). PMID: 26159827    Free PMC article.
Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium.
William J Howat, Fiona M Blows, +49 authors, Montserrat García-Closas.
J Pathol Clin Res, 2015 Jan 01; 1(1). PMID: 27499890    Free PMC article.
High-throughput automated scoring of Ki67 in breast cancer tissue microarrays from the Breast Cancer Association Consortium.
Mustapha Abubakar, William J Howat, +40 authors, Montserrat Garcia-Closas.
J Pathol Clin Res, 2016 Aug 09; 2(3). PMID: 27499923    Free PMC article.
Continuous measurement of breast tumour hormone receptor expression: a comparison of two computational pathology platforms.
Thomas P Ahern, Andrew H Beck, +4 authors, Rulla M Tamimi.
J Clin Pathol, 2016 Oct 13; 70(5). PMID: 27729430    Free PMC article.
Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer.
Xiaolan Feng, Haocheng Li, +9 authors, Alexander Paterson.
Oncotarget, 2016 Oct 16; 7(52). PMID: 27741524    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.
Aldo-Keto Reductase AKR1C1-AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy.
Chen-Ming Zeng, Lin-Lin Chang, +4 authors, Bo Yang.
Front Pharmacol, 2017 Mar 30; 8. PMID: 28352233    Free PMC article.
Review.
Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer.
Linda Zuurbier, Arman Rahman, +23 authors, Ruben Postel.
Oncotarget, 2017 May 11; 8(26). PMID: 28487489    Free PMC article.
Comprehensive DNA methylation study identifies novel progression-related and prognostic markers for cutaneous melanoma.
Jasper Wouters, Miguel Vizoso, +19 authors, Manel Esteller.
BMC Med, 2017 Jun 06; 15(1). PMID: 28578692    Free PMC article.
Whole tumor section quantitative image analysis maximizes between-pathologists' reproducibility for clinical immunohistochemistry-based biomarkers.
Michael Barnes, Chukka Srinivas, +11 authors, Jim Ranger-Moore.
Lab Invest, 2017 Aug 15; 97(12). PMID: 28805805
Validation of immunoexpression of tenascin-C in oral precancerous and cancerous tissues using ImageJ analysis with novel immunohistochemistry profiler plugin: An immunohistochemical quantitative analysis.
Deepa Rajesh Mane, Alka D Kale, Chetan Belaldavar.
J Oral Maxillofac Pathol, 2017 Sep 22; 21(2). PMID: 28932029    Free PMC article.
PD-L1 expression in gastric cancer determined by digital image analyses: pitfalls and correlation with pathologist interpretation.
Han-Na Kim, Jiryeon Jang, +8 authors, Kyoung-Mee Kim.
Virchows Arch, 2019 Aug 30; 476(2). PMID: 31463730
Artificial intelligence in digital breast pathology: Techniques and applications.
Asmaa Ibrahim, Paul Gamble, +4 authors, Emad A Rakha.
Breast, 2020 Jan 15; 49. PMID: 31935669    Free PMC article.
Review.
An Image Analysis Solution For Quantification and Determination of Immunohistochemistry Staining Reproducibility.
Elizabeth A Chlipala, Christine M Bendzinski, +5 authors, Brad Bolon.
Appl Immunohistochem Mol Morphol, 2019 May 15; 28(6). PMID: 31082827    Free PMC article.
Image Analysis in Surgical Pathology.
Mark C Lloyd, James P Monaco, Marilyn M Bui.
Surg Pathol Clin, 2016 Jun 01; 9(2). PMID: 27241112    Free PMC article.
Review.
Artificial Intelligence & Tissue Biomarkers: Advantages, Risks and Perspectives for Pathology.
Cesare Lancellotti, Pierandrea Cancian, +4 authors, Luca Di Tommaso.
Cells, 2021 May 01; 10(4). PMID: 33918173    Free PMC article.
Review.