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Automated assessment of Ki‐67 in breast cancer: the utility of digital image analysis using virtual triple staining and whole slide imaging
Aims Precise evaluation of proliferative activity is essential for the stratified treatment of luminal‐type breast cancer (BC). Immunohistochemical staining of Ki‐67 has been widely used to determine proliferative activity and is recognised to be a useful prognostic marker. However, there remains di...
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Published in: | Histopathology 2020-09, Vol.77 (3), p.471-480 |
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container_title | Histopathology |
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creator | Hida, Akira I Omanovic, Dzenita Pedersen, Lars Oshiro, Yumi Ogura, Takashi Nomura, Tsunehisa Kurebayashi, Junichi Kanomata, Naoki Moriya, Takuya |
description | Aims
Precise evaluation of proliferative activity is essential for the stratified treatment of luminal‐type breast cancer (BC). Immunohistochemical staining of Ki‐67 has been widely used to determine proliferative activity and is recognised to be a useful prognostic marker. However, there remains discussion concerning the methodology. We aimed to develop an automated and reliable Ki‐67 assessment approach for invasive BC.
Materials and results
A retrospective study was designed to include two cohorts consisting of 152 and 261 consecutive patients with luminal‐type BC. Representative tissue blocks following surgery were collected, and three serial sections were stained automatically with Ki‐67, pan‐cytokeratin and p63. The whole slides were scanned digitally and aligned using VirtualTripleStaining – an extension to the VirtualDoubleStaining™ technique provided by Visiopharm software. The aligned files underwent automated invasive cancer detection, hot‐spot identification and Ki‐67 counting. The automated scores showed a significant positive correlation with the pathologists' scores (r = 0.82, P |
doi_str_mv | 10.1111/his.14140 |
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Precise evaluation of proliferative activity is essential for the stratified treatment of luminal‐type breast cancer (BC). Immunohistochemical staining of Ki‐67 has been widely used to determine proliferative activity and is recognised to be a useful prognostic marker. However, there remains discussion concerning the methodology. We aimed to develop an automated and reliable Ki‐67 assessment approach for invasive BC.
Materials and results
A retrospective study was designed to include two cohorts consisting of 152 and 261 consecutive patients with luminal‐type BC. Representative tissue blocks following surgery were collected, and three serial sections were stained automatically with Ki‐67, pan‐cytokeratin and p63. The whole slides were scanned digitally and aligned using VirtualTripleStaining – an extension to the VirtualDoubleStaining™ technique provided by Visiopharm software. The aligned files underwent automated invasive cancer detection, hot‐spot identification and Ki‐67 counting. The automated scores showed a significant positive correlation with the pathologists' scores (r = 0.82, P < 0.0001). Among selected patients with curative surgery and standard adjuvant therapies (n = 130), the digitally assessed low Ki‐67 group (<20%) demonstrated a significantly better prognosis (breast cancer‐specific survival, P = 0.030; hazard ratio = 0.038) than the high Ki‐67 group.
Conclusions
Digital image analysis yielded similar results to the scores determined by experienced pathologists. The prognostic utility was verified in our cohort, and an automated process is expected to have high reproducibility. Although some pitfalls were confirmed and thus need to be monitored by laboratory staff, the application could be utilised for the assessment of BC.</description><identifier>ISSN: 0309-0167</identifier><identifier>EISSN: 1365-2559</identifier><identifier>DOI: 10.1111/his.14140</identifier><language>eng</language><publisher>Oxford: Wiley Subscription Services, Inc</publisher><subject>automated pathology ; Automation ; Breast cancer ; Cytokeratin ; digital image analysis ; Image processing ; Invasiveness ; Ki‐67 ; luminal‐type breast cancer ; Medical prognosis ; Patients ; standardisation ; Surgery ; virtual triple staining</subject><ispartof>Histopathology, 2020-09, Vol.77 (3), p.471-480</ispartof><rights>2020 John Wiley & Sons Ltd</rights><rights>Copyright © 2020 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4000-c1856c83da6ae81c89c528424df6bdf366999f0e6113df0ab6404d01c1ae19463</citedby><cites>FETCH-LOGICAL-c4000-c1856c83da6ae81c89c528424df6bdf366999f0e6113df0ab6404d01c1ae19463</cites><orcidid>0000-0002-4486-8819</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids></links><search><creatorcontrib>Hida, Akira I</creatorcontrib><creatorcontrib>Omanovic, Dzenita</creatorcontrib><creatorcontrib>Pedersen, Lars</creatorcontrib><creatorcontrib>Oshiro, Yumi</creatorcontrib><creatorcontrib>Ogura, Takashi</creatorcontrib><creatorcontrib>Nomura, Tsunehisa</creatorcontrib><creatorcontrib>Kurebayashi, Junichi</creatorcontrib><creatorcontrib>Kanomata, Naoki</creatorcontrib><creatorcontrib>Moriya, Takuya</creatorcontrib><title>Automated assessment of Ki‐67 in breast cancer: the utility of digital image analysis using virtual triple staining and whole slide imaging</title><title>Histopathology</title><description>Aims
Precise evaluation of proliferative activity is essential for the stratified treatment of luminal‐type breast cancer (BC). Immunohistochemical staining of Ki‐67 has been widely used to determine proliferative activity and is recognised to be a useful prognostic marker. However, there remains discussion concerning the methodology. We aimed to develop an automated and reliable Ki‐67 assessment approach for invasive BC.
Materials and results
A retrospective study was designed to include two cohorts consisting of 152 and 261 consecutive patients with luminal‐type BC. Representative tissue blocks following surgery were collected, and three serial sections were stained automatically with Ki‐67, pan‐cytokeratin and p63. The whole slides were scanned digitally and aligned using VirtualTripleStaining – an extension to the VirtualDoubleStaining™ technique provided by Visiopharm software. The aligned files underwent automated invasive cancer detection, hot‐spot identification and Ki‐67 counting. The automated scores showed a significant positive correlation with the pathologists' scores (r = 0.82, P < 0.0001). Among selected patients with curative surgery and standard adjuvant therapies (n = 130), the digitally assessed low Ki‐67 group (<20%) demonstrated a significantly better prognosis (breast cancer‐specific survival, P = 0.030; hazard ratio = 0.038) than the high Ki‐67 group.
Conclusions
Digital image analysis yielded similar results to the scores determined by experienced pathologists. The prognostic utility was verified in our cohort, and an automated process is expected to have high reproducibility. Although some pitfalls were confirmed and thus need to be monitored by laboratory staff, the application could be utilised for the assessment of BC.</description><subject>automated pathology</subject><subject>Automation</subject><subject>Breast cancer</subject><subject>Cytokeratin</subject><subject>digital image analysis</subject><subject>Image processing</subject><subject>Invasiveness</subject><subject>Ki‐67</subject><subject>luminal‐type breast cancer</subject><subject>Medical prognosis</subject><subject>Patients</subject><subject>standardisation</subject><subject>Surgery</subject><subject>virtual triple staining</subject><issn>0309-0167</issn><issn>1365-2559</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp10cFq3DAQBmBRUuhm20PfQNBLcnCisWStnVsIabI00EPbs9FK410Frb3VyFl86wsE8ox5ktjZnArRRfDrG8HwM_YVxBmM53zj6QwUKPGBzUDqIsuLojpiMyFFlQnQi0_smOheCFjIPJ-xx8s-dVuT0HFDhERbbBPvGv7DP_970gvuW76KaChxa1qL8YKnDfI--eDTMEHn1z6ZwP3WrJGb1oSBPPGefLvmDz6mfnxM0e8CckrGt1NuWsf3m26Kgnf4Ojzmn9nHxgTCL2_3nP35fv376ja7-3mzvLq8y6wSQmQWykLbUjqjDZZgy8oWealy5Rq9co3UuqqqRqAGkK4RZqWVUE6ABYNQKS3n7OTw7y52f3ukVG89WQzBtNj1VOcKdCUhLyb67T963_Vx3HJSCkq1kFKM6vSgbOyIIjb1Lo47xaEGUU_F1GMx9Wsxoz0_2L0POLwP69vlr8PEC_CokQ8</recordid><startdate>202009</startdate><enddate>202009</enddate><creator>Hida, Akira I</creator><creator>Omanovic, Dzenita</creator><creator>Pedersen, Lars</creator><creator>Oshiro, Yumi</creator><creator>Ogura, Takashi</creator><creator>Nomura, Tsunehisa</creator><creator>Kurebayashi, Junichi</creator><creator>Kanomata, Naoki</creator><creator>Moriya, Takuya</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4486-8819</orcidid></search><sort><creationdate>202009</creationdate><title>Automated assessment of Ki‐67 in breast cancer: the utility of digital image analysis using virtual triple staining and whole slide imaging</title><author>Hida, Akira I ; Omanovic, Dzenita ; Pedersen, Lars ; Oshiro, Yumi ; Ogura, Takashi ; Nomura, Tsunehisa ; Kurebayashi, Junichi ; Kanomata, Naoki ; Moriya, Takuya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4000-c1856c83da6ae81c89c528424df6bdf366999f0e6113df0ab6404d01c1ae19463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>automated pathology</topic><topic>Automation</topic><topic>Breast cancer</topic><topic>Cytokeratin</topic><topic>digital image analysis</topic><topic>Image processing</topic><topic>Invasiveness</topic><topic>Ki‐67</topic><topic>luminal‐type breast cancer</topic><topic>Medical prognosis</topic><topic>Patients</topic><topic>standardisation</topic><topic>Surgery</topic><topic>virtual triple staining</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hida, Akira I</creatorcontrib><creatorcontrib>Omanovic, Dzenita</creatorcontrib><creatorcontrib>Pedersen, Lars</creatorcontrib><creatorcontrib>Oshiro, Yumi</creatorcontrib><creatorcontrib>Ogura, Takashi</creatorcontrib><creatorcontrib>Nomura, Tsunehisa</creatorcontrib><creatorcontrib>Kurebayashi, Junichi</creatorcontrib><creatorcontrib>Kanomata, Naoki</creatorcontrib><creatorcontrib>Moriya, Takuya</creatorcontrib><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Histopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hida, Akira I</au><au>Omanovic, Dzenita</au><au>Pedersen, Lars</au><au>Oshiro, Yumi</au><au>Ogura, Takashi</au><au>Nomura, Tsunehisa</au><au>Kurebayashi, Junichi</au><au>Kanomata, Naoki</au><au>Moriya, Takuya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Automated assessment of Ki‐67 in breast cancer: the utility of digital image analysis using virtual triple staining and whole slide imaging</atitle><jtitle>Histopathology</jtitle><date>2020-09</date><risdate>2020</risdate><volume>77</volume><issue>3</issue><spage>471</spage><epage>480</epage><pages>471-480</pages><issn>0309-0167</issn><eissn>1365-2559</eissn><abstract>Aims
Precise evaluation of proliferative activity is essential for the stratified treatment of luminal‐type breast cancer (BC). Immunohistochemical staining of Ki‐67 has been widely used to determine proliferative activity and is recognised to be a useful prognostic marker. However, there remains discussion concerning the methodology. We aimed to develop an automated and reliable Ki‐67 assessment approach for invasive BC.
Materials and results
A retrospective study was designed to include two cohorts consisting of 152 and 261 consecutive patients with luminal‐type BC. Representative tissue blocks following surgery were collected, and three serial sections were stained automatically with Ki‐67, pan‐cytokeratin and p63. The whole slides were scanned digitally and aligned using VirtualTripleStaining – an extension to the VirtualDoubleStaining™ technique provided by Visiopharm software. The aligned files underwent automated invasive cancer detection, hot‐spot identification and Ki‐67 counting. The automated scores showed a significant positive correlation with the pathologists' scores (r = 0.82, P < 0.0001). Among selected patients with curative surgery and standard adjuvant therapies (n = 130), the digitally assessed low Ki‐67 group (<20%) demonstrated a significantly better prognosis (breast cancer‐specific survival, P = 0.030; hazard ratio = 0.038) than the high Ki‐67 group.
Conclusions
Digital image analysis yielded similar results to the scores determined by experienced pathologists. The prognostic utility was verified in our cohort, and an automated process is expected to have high reproducibility. Although some pitfalls were confirmed and thus need to be monitored by laboratory staff, the application could be utilised for the assessment of BC.</abstract><cop>Oxford</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1111/his.14140</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-4486-8819</orcidid></addata></record> |
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subjects | automated pathology Automation Breast cancer Cytokeratin digital image analysis Image processing Invasiveness Ki‐67 luminal‐type breast cancer Medical prognosis Patients standardisation Surgery virtual triple staining |
title | Automated assessment of Ki‐67 in breast cancer: the utility of digital image analysis using virtual triple staining and whole slide imaging |
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