Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists
Background Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical e...
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| Veröffentlicht in: | Breast cancer (Tokyo, Japan) Japan), 2018-11, Vol.25 (6), p.768-777 |
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| creator | Morioka, Toru Niikura, Naoki Kumaki, Nobue Masuda, Shinobu Iwamoto, Takayuki Yokoyama, Kozue Ogiya, Rin Oshitanai, Risa Terao, Mayako Tsuda, Banri Okamura, Takuho Saito, Yuki Suzuki, Yasuhiro Tokuda, Yutaka |
| description | Background
Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown.
Methods
We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist’s scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan–Meier method and compared using the log-rank test.
Results
Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist’s scoring for all patients (
κ
0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (
p
|
| doi_str_mv | 10.1007/s12282-018-0885-1 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2062838732</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A712280129</galeid><sourcerecordid>A712280129</sourcerecordid><originalsourceid>FETCH-LOGICAL-c435t-2016de82cb2a2837f400aefc00f24a22d456d12aa88e057c7507f64ee19a57f73</originalsourceid><addsrcrecordid>eNp9kc1q3TAQhUVpaNK0D9BNEXTTjZORbEvyMlzSHxrIJl0LXXvkKNiWq7Gh9-0r47RQKEULDdJ3DsM5jL0TcCUA9DUJKY0sQJgCjKkL8YJdCGOgqGRZvsxzWUGhjDLn7DXRE0BValCv2LlsmrpRpbpgj4c4zi4FihOPnn8LhdJ8cEccwtTzMHX4k4_oaE044rQQX2n76EIfFjfwMLoeuZvccKJAeeg4tTFtyPHEZ7c8xiH2gRZ6w868GwjfPt-X7Pun24fDl-Lu_vPXw81d0VZlvRQShOrQyPYonTSl9hWAQ98CeFk5KbuqVp2QzhmDUOtW16C9qhBF42rtdXnJPu6-c4o_VqTFjoFaHAY3YVzJSlDZ1-hSZvTDjvZuQBsmH5fk2g23N3qLFoRsMnX1DyqfDsfQxgl9yO9_CcQuaFMkSujtnHJO6WQF2K03u_dmc292682KrHn_vPV6HLH7o_hdVAbkDtC8pYvJPsU15dzpP66_ADtuoew</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2062838732</pqid></control><display><type>article</type><title>Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Morioka, Toru ; Niikura, Naoki ; Kumaki, Nobue ; Masuda, Shinobu ; Iwamoto, Takayuki ; Yokoyama, Kozue ; Ogiya, Rin ; Oshitanai, Risa ; Terao, Mayako ; Tsuda, Banri ; Okamura, Takuho ; Saito, Yuki ; Suzuki, Yasuhiro ; Tokuda, Yutaka</creator><creatorcontrib>Morioka, Toru ; Niikura, Naoki ; Kumaki, Nobue ; Masuda, Shinobu ; Iwamoto, Takayuki ; Yokoyama, Kozue ; Ogiya, Rin ; Oshitanai, Risa ; Terao, Mayako ; Tsuda, Banri ; Okamura, Takuho ; Saito, Yuki ; Suzuki, Yasuhiro ; Tokuda, Yutaka</creatorcontrib><description>Background
Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown.
Methods
We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist’s scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan–Meier method and compared using the log-rank test.
Results
Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist’s scoring for all patients (
κ
0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (
p
< 0.001) and obtained using image analysis (
p
= 0.031).
Conclusions
The Ki-67 indices obtained using image analysis were moderately correlated with those scored by pathologists. Digital image analysis can be effective for measuring Ki-67 values, because they are associated with relapse-free survival in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and patients at stage I or II.</description><identifier>ISSN: 1340-6868</identifier><identifier>EISSN: 1880-4233</identifier><identifier>DOI: 10.1007/s12282-018-0885-1</identifier><identifier>PMID: 29959636</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Analysis ; Breast Neoplasms - chemistry ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Cancer Research ; Equipment and supplies ; Estrogen ; Female ; Health aspects ; Humans ; Image processing ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Ki-67 Antigen - analysis ; Medical colleges ; Medicine ; Medicine & Public Health ; Middle Aged ; Neoplasm Staging ; Oncology ; Original Article ; Pathologists ; Receptor, ErbB-2 - analysis ; Receptors, Estrogen - analysis ; Retrospective Studies ; Surgery ; Surgical Oncology ; Women</subject><ispartof>Breast cancer (Tokyo, Japan), 2018-11, Vol.25 (6), p.768-777</ispartof><rights>The Japanese Breast Cancer Society 2018</rights><rights>COPYRIGHT 2018 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-2016de82cb2a2837f400aefc00f24a22d456d12aa88e057c7507f64ee19a57f73</citedby><cites>FETCH-LOGICAL-c435t-2016de82cb2a2837f400aefc00f24a22d456d12aa88e057c7507f64ee19a57f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12282-018-0885-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12282-018-0885-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29959636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morioka, Toru</creatorcontrib><creatorcontrib>Niikura, Naoki</creatorcontrib><creatorcontrib>Kumaki, Nobue</creatorcontrib><creatorcontrib>Masuda, Shinobu</creatorcontrib><creatorcontrib>Iwamoto, Takayuki</creatorcontrib><creatorcontrib>Yokoyama, Kozue</creatorcontrib><creatorcontrib>Ogiya, Rin</creatorcontrib><creatorcontrib>Oshitanai, Risa</creatorcontrib><creatorcontrib>Terao, Mayako</creatorcontrib><creatorcontrib>Tsuda, Banri</creatorcontrib><creatorcontrib>Okamura, Takuho</creatorcontrib><creatorcontrib>Saito, Yuki</creatorcontrib><creatorcontrib>Suzuki, Yasuhiro</creatorcontrib><creatorcontrib>Tokuda, Yutaka</creatorcontrib><title>Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists</title><title>Breast cancer (Tokyo, Japan)</title><addtitle>Breast Cancer</addtitle><addtitle>Breast Cancer</addtitle><description>Background
Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown.
Methods
We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist’s scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan–Meier method and compared using the log-rank test.
Results
Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist’s scoring for all patients (
κ
0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (
p
< 0.001) and obtained using image analysis (
p
= 0.031).
Conclusions
The Ki-67 indices obtained using image analysis were moderately correlated with those scored by pathologists. Digital image analysis can be effective for measuring Ki-67 values, because they are associated with relapse-free survival in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and patients at stage I or II.</description><subject>Analysis</subject><subject>Breast Neoplasms - chemistry</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer Research</subject><subject>Equipment and supplies</subject><subject>Estrogen</subject><subject>Female</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Image processing</subject><subject>Image Processing, Computer-Assisted</subject><subject>Immunohistochemistry</subject><subject>Ki-67 Antigen - analysis</subject><subject>Medical colleges</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Pathologists</subject><subject>Receptor, ErbB-2 - analysis</subject><subject>Receptors, Estrogen - analysis</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Women</subject><issn>1340-6868</issn><issn>1880-4233</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1q3TAQhUVpaNK0D9BNEXTTjZORbEvyMlzSHxrIJl0LXXvkKNiWq7Gh9-0r47RQKEULDdJ3DsM5jL0TcCUA9DUJKY0sQJgCjKkL8YJdCGOgqGRZvsxzWUGhjDLn7DXRE0BValCv2LlsmrpRpbpgj4c4zi4FihOPnn8LhdJ8cEccwtTzMHX4k4_oaE044rQQX2n76EIfFjfwMLoeuZvccKJAeeg4tTFtyPHEZ7c8xiH2gRZ6w868GwjfPt-X7Pun24fDl-Lu_vPXw81d0VZlvRQShOrQyPYonTSl9hWAQ98CeFk5KbuqVp2QzhmDUOtW16C9qhBF42rtdXnJPu6-c4o_VqTFjoFaHAY3YVzJSlDZ1-hSZvTDjvZuQBsmH5fk2g23N3qLFoRsMnX1DyqfDsfQxgl9yO9_CcQuaFMkSujtnHJO6WQF2K03u_dmc292682KrHn_vPV6HLH7o_hdVAbkDtC8pYvJPsU15dzpP66_ADtuoew</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Morioka, Toru</creator><creator>Niikura, Naoki</creator><creator>Kumaki, Nobue</creator><creator>Masuda, Shinobu</creator><creator>Iwamoto, Takayuki</creator><creator>Yokoyama, Kozue</creator><creator>Ogiya, Rin</creator><creator>Oshitanai, Risa</creator><creator>Terao, Mayako</creator><creator>Tsuda, Banri</creator><creator>Okamura, Takuho</creator><creator>Saito, Yuki</creator><creator>Suzuki, Yasuhiro</creator><creator>Tokuda, Yutaka</creator><general>Springer Japan</general><general>Springer</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20181101</creationdate><title>Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists</title><author>Morioka, Toru ; Niikura, Naoki ; Kumaki, Nobue ; Masuda, Shinobu ; Iwamoto, Takayuki ; Yokoyama, Kozue ; Ogiya, Rin ; Oshitanai, Risa ; Terao, Mayako ; Tsuda, Banri ; Okamura, Takuho ; Saito, Yuki ; Suzuki, Yasuhiro ; Tokuda, Yutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-2016de82cb2a2837f400aefc00f24a22d456d12aa88e057c7507f64ee19a57f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Analysis</topic><topic>Breast Neoplasms - chemistry</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer Research</topic><topic>Equipment and supplies</topic><topic>Estrogen</topic><topic>Female</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Image processing</topic><topic>Image Processing, Computer-Assisted</topic><topic>Immunohistochemistry</topic><topic>Ki-67 Antigen - analysis</topic><topic>Medical colleges</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Pathologists</topic><topic>Receptor, ErbB-2 - analysis</topic><topic>Receptors, Estrogen - analysis</topic><topic>Retrospective Studies</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Women</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morioka, Toru</creatorcontrib><creatorcontrib>Niikura, Naoki</creatorcontrib><creatorcontrib>Kumaki, Nobue</creatorcontrib><creatorcontrib>Masuda, Shinobu</creatorcontrib><creatorcontrib>Iwamoto, Takayuki</creatorcontrib><creatorcontrib>Yokoyama, Kozue</creatorcontrib><creatorcontrib>Ogiya, Rin</creatorcontrib><creatorcontrib>Oshitanai, Risa</creatorcontrib><creatorcontrib>Terao, Mayako</creatorcontrib><creatorcontrib>Tsuda, Banri</creatorcontrib><creatorcontrib>Okamura, Takuho</creatorcontrib><creatorcontrib>Saito, Yuki</creatorcontrib><creatorcontrib>Suzuki, Yasuhiro</creatorcontrib><creatorcontrib>Tokuda, Yutaka</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Breast cancer (Tokyo, Japan)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morioka, Toru</au><au>Niikura, Naoki</au><au>Kumaki, Nobue</au><au>Masuda, Shinobu</au><au>Iwamoto, Takayuki</au><au>Yokoyama, Kozue</au><au>Ogiya, Rin</au><au>Oshitanai, Risa</au><au>Terao, Mayako</au><au>Tsuda, Banri</au><au>Okamura, Takuho</au><au>Saito, Yuki</au><au>Suzuki, Yasuhiro</au><au>Tokuda, Yutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists</atitle><jtitle>Breast cancer (Tokyo, Japan)</jtitle><stitle>Breast Cancer</stitle><addtitle>Breast Cancer</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>25</volume><issue>6</issue><spage>768</spage><epage>777</epage><pages>768-777</pages><issn>1340-6868</issn><eissn>1880-4233</eissn><abstract>Background
Routine analysis of Ki-67 is not widely recommended for clinical decision-making because of poor reproducibility. Furthermore, counting numerous cells can be laborious for pathologists. Digital image analysis for immunohistochemical analysis was recently developed; however, the clinical efficacy of the Ki-67 index obtained using image analysis is unknown.
Methods
We retrospectively identified female patients with breast cancer with immunohistochemical Ki-67 and survival data using the pathology database at the Tokai University, Japan. Ki-67 expression was scored by three pathologists. Slides were scanned and converted to virtual slides; Ki-67-positive cells were counted using image analysis. Ki-67 indices obtained by the pathologist’s scoring and image analysis were evaluated by 2 × 2 analysis. Relationships between Ki-67 index and survival outcomes were evaluated using the Kaplan–Meier method and compared using the log-rank test.
Results
Based on the 2 × 2 analysis, Ki-67 index obtained using image analysis was moderately correlated with the pathologist’s scoring for all patients (
κ
0.41; sensitivity, 0.573; specificity, 0.878). Poorer relapse-free survival was associated with high Ki-67 index than with low Ki-67 index for estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and stage I or II patients scored by pathologists (
p
< 0.001) and obtained using image analysis (
p
= 0.031).
Conclusions
The Ki-67 indices obtained using image analysis were moderately correlated with those scored by pathologists. Digital image analysis can be effective for measuring Ki-67 values, because they are associated with relapse-free survival in estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and patients at stage I or II.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>29959636</pmid><doi>10.1007/s12282-018-0885-1</doi><tpages>10</tpages></addata></record> |
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| issn | 1340-6868 1880-4233 |
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| subjects | Analysis Breast Neoplasms - chemistry Breast Neoplasms - mortality Breast Neoplasms - pathology Cancer Research Equipment and supplies Estrogen Female Health aspects Humans Image processing Image Processing, Computer-Assisted Immunohistochemistry Ki-67 Antigen - analysis Medical colleges Medicine Medicine & Public Health Middle Aged Neoplasm Staging Oncology Original Article Pathologists Receptor, ErbB-2 - analysis Receptors, Estrogen - analysis Retrospective Studies Surgery Surgical Oncology Women |
| title | Comparison of Ki-67 labeling index measurements using digital image analysis and scoring by pathologists |
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