Comparison of the methods for measuring the Ki-67 labeling index in adrenocortical carcinoma: manual versus digital image analysis
Summary Adrenocortical carcinoma (ACC) is a rare, highly malignant neoplasm harboring marked histologic heterogeneity. The Ki-67 labeling index (LI) is one of the most effective diagnostic and prognostic markers in ACC. However, its assessment has by no means been standardized. Therefore, in this st...
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| Veröffentlicht in: | Human pathology 2016-07, Vol.53, p.41-50 |
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| creator | Yamazaki, Yuto, MD Nakamura, Yasuhiro, MD, PhD Shibahara, Yukiko, MD, PhD Konosu-Fukaya, Sachiko, MD Sato, Naomi, MD Kubota, Fumie, MD Oki, Yutaka, MD, PhD Baba, Satoshi, MD, PhD Midorikawa, Sanae, MD, PhD Morimoto, Ryo, MD, PhD Satoh, Fumitoshi, MD, PhD Sasano, Hironobu, MD, PhD |
| description | Summary Adrenocortical carcinoma (ACC) is a rare, highly malignant neoplasm harboring marked histologic heterogeneity. The Ki-67 labeling index (LI) is one of the most effective diagnostic and prognostic markers in ACC. However, its assessment has by no means been standardized. Therefore, in this study, we analyzed the Ki-67 LI in 18 ACC cases both by seven pathologists using microscopes (MA; manual analysis) and with digital image analysis (DIA) and also compared the Ki-67 LI obtained by selecting “hot spots” and formulating the “average” reading of the whole tumor specimen. In addition, we performed statistical analysis of the association between Ki-67 LI and the clinical and pathologic features of individual cases. The DIA was significantly correlated with MA in hot spots but not in the average fields. The Ki-67 LI in hot spots was significantly and consistently higher than that in average areas by both MA and DIA, indicating intratumoral heterogeneity. The Ki-67 LI was significantly correlated with the Weiss criteria (eosinophilic cytoplasm, nuclear atypia, atypical mitoses, and sinusoidal invasion) by any mode of evaluation. The clinical outcome was significantly better in the patients with a Ki-67 < 10% than in those with a Ki-67 > 10% by MA in hot spots. The Ki-67 LI in hot spots measured by MA best reflected the clinical and pathologic features of ACC. Employment of DIA to obtain the Ki-67 LI in ACC requires further improvement, including correction of its overestimation of the value by counting non-tumorous cells and nuclear segmentation in areas of high cell density. |
| doi_str_mv | 10.1016/j.humpath.2015.10.017 |
| format | Article |
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The Ki-67 labeling index (LI) is one of the most effective diagnostic and prognostic markers in ACC. However, its assessment has by no means been standardized. Therefore, in this study, we analyzed the Ki-67 LI in 18 ACC cases both by seven pathologists using microscopes (MA; manual analysis) and with digital image analysis (DIA) and also compared the Ki-67 LI obtained by selecting “hot spots” and formulating the “average” reading of the whole tumor specimen. In addition, we performed statistical analysis of the association between Ki-67 LI and the clinical and pathologic features of individual cases. The DIA was significantly correlated with MA in hot spots but not in the average fields. The Ki-67 LI in hot spots was significantly and consistently higher than that in average areas by both MA and DIA, indicating intratumoral heterogeneity. The Ki-67 LI was significantly correlated with the Weiss criteria (eosinophilic cytoplasm, nuclear atypia, atypical mitoses, and sinusoidal invasion) by any mode of evaluation. The clinical outcome was significantly better in the patients with a Ki-67 < 10% than in those with a Ki-67 > 10% by MA in hot spots. The Ki-67 LI in hot spots measured by MA best reflected the clinical and pathologic features of ACC. Employment of DIA to obtain the Ki-67 LI in ACC requires further improvement, including correction of its overestimation of the value by counting non-tumorous cells and nuclear segmentation in areas of high cell density.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2015.10.017</identifier><identifier>PMID: 26980031</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adrenal Cortex Neoplasms - chemistry ; Adrenal Cortex Neoplasms - mortality ; Adrenal Cortex Neoplasms - pathology ; Adrenal Cortex Neoplasms - therapy ; Adrenocortical carcinoma ; Adrenocortical Carcinoma - chemistry ; Adrenocortical Carcinoma - mortality ; Adrenocortical Carcinoma - pathology ; Adrenocortical Carcinoma - therapy ; Adult ; Aged ; Automation, Laboratory ; Breast cancer ; Cell Proliferation ; Chemotherapy ; Child ; Digital image analysis ; Disease-Free Survival ; Female ; Humans ; Image Interpretation, Computer-Assisted - methods ; Immunohistochemistry ; Infant, Newborn ; Japan ; Kaplan-Meier Estimate ; Ki-67 Antigen - analysis ; Ki-67 labeling index ; Labeling ; Male ; Metastasis ; Microscopy ; Middle Aged ; Neoplasm Staging ; Observer Variation ; Pathology ; Predictive Value of Tests ; Reproducibility of Results ; Time Factors ; Treatment Outcome ; Tumors ; Weiss criteria</subject><ispartof>Human pathology, 2016-07, Vol.53, p.41-50</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Jul 01, 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-c38c58350a9b2b856556674b7c973a7a758761c092d39d4f1a6798f61ff14d7c3</citedby><cites>FETCH-LOGICAL-c514t-c38c58350a9b2b856556674b7c973a7a758761c092d39d4f1a6798f61ff14d7c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0046817716000721$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26980031$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamazaki, Yuto, MD</creatorcontrib><creatorcontrib>Nakamura, Yasuhiro, MD, PhD</creatorcontrib><creatorcontrib>Shibahara, Yukiko, MD, PhD</creatorcontrib><creatorcontrib>Konosu-Fukaya, Sachiko, MD</creatorcontrib><creatorcontrib>Sato, Naomi, MD</creatorcontrib><creatorcontrib>Kubota, Fumie, MD</creatorcontrib><creatorcontrib>Oki, Yutaka, MD, PhD</creatorcontrib><creatorcontrib>Baba, Satoshi, MD, PhD</creatorcontrib><creatorcontrib>Midorikawa, Sanae, MD, PhD</creatorcontrib><creatorcontrib>Morimoto, Ryo, MD, PhD</creatorcontrib><creatorcontrib>Satoh, Fumitoshi, MD, PhD</creatorcontrib><creatorcontrib>Sasano, Hironobu, MD, PhD</creatorcontrib><title>Comparison of the methods for measuring the Ki-67 labeling index in adrenocortical carcinoma: manual versus digital image analysis</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary Adrenocortical carcinoma (ACC) is a rare, highly malignant neoplasm harboring marked histologic heterogeneity. The Ki-67 labeling index (LI) is one of the most effective diagnostic and prognostic markers in ACC. However, its assessment has by no means been standardized. Therefore, in this study, we analyzed the Ki-67 LI in 18 ACC cases both by seven pathologists using microscopes (MA; manual analysis) and with digital image analysis (DIA) and also compared the Ki-67 LI obtained by selecting “hot spots” and formulating the “average” reading of the whole tumor specimen. In addition, we performed statistical analysis of the association between Ki-67 LI and the clinical and pathologic features of individual cases. The DIA was significantly correlated with MA in hot spots but not in the average fields. The Ki-67 LI in hot spots was significantly and consistently higher than that in average areas by both MA and DIA, indicating intratumoral heterogeneity. The Ki-67 LI was significantly correlated with the Weiss criteria (eosinophilic cytoplasm, nuclear atypia, atypical mitoses, and sinusoidal invasion) by any mode of evaluation. The clinical outcome was significantly better in the patients with a Ki-67 < 10% than in those with a Ki-67 > 10% by MA in hot spots. The Ki-67 LI in hot spots measured by MA best reflected the clinical and pathologic features of ACC. Employment of DIA to obtain the Ki-67 LI in ACC requires further improvement, including correction of its overestimation of the value by counting non-tumorous cells and nuclear segmentation in areas of high cell density.</description><subject>Adrenal Cortex Neoplasms - chemistry</subject><subject>Adrenal Cortex Neoplasms - mortality</subject><subject>Adrenal Cortex Neoplasms - pathology</subject><subject>Adrenal Cortex Neoplasms - therapy</subject><subject>Adrenocortical carcinoma</subject><subject>Adrenocortical Carcinoma - chemistry</subject><subject>Adrenocortical Carcinoma - mortality</subject><subject>Adrenocortical Carcinoma - pathology</subject><subject>Adrenocortical Carcinoma - therapy</subject><subject>Adult</subject><subject>Aged</subject><subject>Automation, Laboratory</subject><subject>Breast cancer</subject><subject>Cell Proliferation</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Digital image analysis</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Humans</subject><subject>Image Interpretation, Computer-Assisted - methods</subject><subject>Immunohistochemistry</subject><subject>Infant, Newborn</subject><subject>Japan</subject><subject>Kaplan-Meier Estimate</subject><subject>Ki-67 Antigen - analysis</subject><subject>Ki-67 labeling index</subject><subject>Labeling</subject><subject>Male</subject><subject>Metastasis</subject><subject>Microscopy</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Observer Variation</subject><subject>Pathology</subject><subject>Predictive Value of Tests</subject><subject>Reproducibility of Results</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Weiss criteria</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2P0zAQhi0EYrsLPwFkiQuXFI8T2wkHEKpYQKzEAThbjj1pXZK42MmKXvnlOLSAtBcu_hg_89qedwh5AmwNDOSL_Xo3Dwcz7dacgcixNQN1j6xAlLyoy4bfJyvGKlnUoNQFuUxpzxiAqMRDcsFlUzNWwor83ISsEn0KIw0dnXZIB5x2wSXahZjXJs3Rj9vfJx99IRXtTYv9EvKjwx95pMZFHIMNcfLW9NSaaP0YBvOSDmacc-QWY5oTdX7rp7z1g9kiNaPpj8mnR-RBZ_qEj8_zFfl6_fbL5n1x8-ndh82bm8IKqKbClrUVdSmYaVre1kIKIaWqWmUbVRpllKiVBMsa7srGVR0YqZq6k9B1UDllyyvy_KR7iOH7jGnSg08W-96MGOakIeOKcyllRp_dQfdhjvm9mcqFqwSrmMiUOFE2hpQidvoQ89fiUQPTi0l6r88m6cWkJZxNynlPz-pzO6D7m_XHlQy8PgGYy3HrMepkPY4WnY9oJ-2C_-8Vr-4o2GzZ4s43PGL69xuduGb689IpS6OAZIwpDuUvUmy6fA</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Yamazaki, Yuto, MD</creator><creator>Nakamura, Yasuhiro, MD, PhD</creator><creator>Shibahara, Yukiko, MD, PhD</creator><creator>Konosu-Fukaya, Sachiko, MD</creator><creator>Sato, Naomi, MD</creator><creator>Kubota, Fumie, MD</creator><creator>Oki, Yutaka, MD, PhD</creator><creator>Baba, Satoshi, MD, PhD</creator><creator>Midorikawa, Sanae, MD, PhD</creator><creator>Morimoto, Ryo, MD, PhD</creator><creator>Satoh, Fumitoshi, MD, PhD</creator><creator>Sasano, Hironobu, MD, PhD</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>K9.</scope><scope>7X8</scope></search><sort><creationdate>20160701</creationdate><title>Comparison of the methods for measuring the Ki-67 labeling index in adrenocortical carcinoma: manual versus digital image analysis</title><author>Yamazaki, Yuto, MD ; Nakamura, Yasuhiro, MD, PhD ; Shibahara, Yukiko, MD, PhD ; Konosu-Fukaya, Sachiko, MD ; Sato, Naomi, MD ; Kubota, Fumie, MD ; Oki, Yutaka, MD, PhD ; Baba, Satoshi, MD, PhD ; Midorikawa, Sanae, MD, PhD ; Morimoto, Ryo, MD, PhD ; Satoh, Fumitoshi, MD, PhD ; Sasano, Hironobu, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-c38c58350a9b2b856556674b7c973a7a758761c092d39d4f1a6798f61ff14d7c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adrenal Cortex Neoplasms - chemistry</topic><topic>Adrenal Cortex Neoplasms - mortality</topic><topic>Adrenal Cortex Neoplasms - pathology</topic><topic>Adrenal Cortex Neoplasms - therapy</topic><topic>Adrenocortical carcinoma</topic><topic>Adrenocortical Carcinoma - chemistry</topic><topic>Adrenocortical Carcinoma - mortality</topic><topic>Adrenocortical Carcinoma - pathology</topic><topic>Adrenocortical Carcinoma - therapy</topic><topic>Adult</topic><topic>Aged</topic><topic>Automation, Laboratory</topic><topic>Breast cancer</topic><topic>Cell Proliferation</topic><topic>Chemotherapy</topic><topic>Child</topic><topic>Digital image analysis</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Humans</topic><topic>Image Interpretation, Computer-Assisted - methods</topic><topic>Immunohistochemistry</topic><topic>Infant, Newborn</topic><topic>Japan</topic><topic>Kaplan-Meier Estimate</topic><topic>Ki-67 Antigen - analysis</topic><topic>Ki-67 labeling index</topic><topic>Labeling</topic><topic>Male</topic><topic>Metastasis</topic><topic>Microscopy</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Observer Variation</topic><topic>Pathology</topic><topic>Predictive Value of Tests</topic><topic>Reproducibility of Results</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Weiss criteria</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamazaki, Yuto, MD</creatorcontrib><creatorcontrib>Nakamura, Yasuhiro, MD, PhD</creatorcontrib><creatorcontrib>Shibahara, Yukiko, MD, PhD</creatorcontrib><creatorcontrib>Konosu-Fukaya, Sachiko, MD</creatorcontrib><creatorcontrib>Sato, Naomi, MD</creatorcontrib><creatorcontrib>Kubota, Fumie, MD</creatorcontrib><creatorcontrib>Oki, Yutaka, MD, PhD</creatorcontrib><creatorcontrib>Baba, Satoshi, MD, PhD</creatorcontrib><creatorcontrib>Midorikawa, Sanae, MD, PhD</creatorcontrib><creatorcontrib>Morimoto, Ryo, MD, PhD</creatorcontrib><creatorcontrib>Satoh, Fumitoshi, MD, PhD</creatorcontrib><creatorcontrib>Sasano, Hironobu, MD, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamazaki, Yuto, MD</au><au>Nakamura, Yasuhiro, MD, PhD</au><au>Shibahara, Yukiko, MD, PhD</au><au>Konosu-Fukaya, Sachiko, MD</au><au>Sato, Naomi, MD</au><au>Kubota, Fumie, MD</au><au>Oki, Yutaka, MD, PhD</au><au>Baba, Satoshi, MD, PhD</au><au>Midorikawa, Sanae, MD, PhD</au><au>Morimoto, Ryo, MD, PhD</au><au>Satoh, Fumitoshi, MD, PhD</au><au>Sasano, Hironobu, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of the methods for measuring the Ki-67 labeling index in adrenocortical carcinoma: manual versus digital image analysis</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>53</volume><spage>41</spage><epage>50</epage><pages>41-50</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>Summary Adrenocortical carcinoma (ACC) is a rare, highly malignant neoplasm harboring marked histologic heterogeneity. The Ki-67 labeling index (LI) is one of the most effective diagnostic and prognostic markers in ACC. However, its assessment has by no means been standardized. Therefore, in this study, we analyzed the Ki-67 LI in 18 ACC cases both by seven pathologists using microscopes (MA; manual analysis) and with digital image analysis (DIA) and also compared the Ki-67 LI obtained by selecting “hot spots” and formulating the “average” reading of the whole tumor specimen. In addition, we performed statistical analysis of the association between Ki-67 LI and the clinical and pathologic features of individual cases. The DIA was significantly correlated with MA in hot spots but not in the average fields. The Ki-67 LI in hot spots was significantly and consistently higher than that in average areas by both MA and DIA, indicating intratumoral heterogeneity. The Ki-67 LI was significantly correlated with the Weiss criteria (eosinophilic cytoplasm, nuclear atypia, atypical mitoses, and sinusoidal invasion) by any mode of evaluation. The clinical outcome was significantly better in the patients with a Ki-67 < 10% than in those with a Ki-67 > 10% by MA in hot spots. The Ki-67 LI in hot spots measured by MA best reflected the clinical and pathologic features of ACC. Employment of DIA to obtain the Ki-67 LI in ACC requires further improvement, including correction of its overestimation of the value by counting non-tumorous cells and nuclear segmentation in areas of high cell density.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26980031</pmid><doi>10.1016/j.humpath.2015.10.017</doi><tpages>10</tpages></addata></record> |
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| subjects | Adrenal Cortex Neoplasms - chemistry Adrenal Cortex Neoplasms - mortality Adrenal Cortex Neoplasms - pathology Adrenal Cortex Neoplasms - therapy Adrenocortical carcinoma Adrenocortical Carcinoma - chemistry Adrenocortical Carcinoma - mortality Adrenocortical Carcinoma - pathology Adrenocortical Carcinoma - therapy Adult Aged Automation, Laboratory Breast cancer Cell Proliferation Chemotherapy Child Digital image analysis Disease-Free Survival Female Humans Image Interpretation, Computer-Assisted - methods Immunohistochemistry Infant, Newborn Japan Kaplan-Meier Estimate Ki-67 Antigen - analysis Ki-67 labeling index Labeling Male Metastasis Microscopy Middle Aged Neoplasm Staging Observer Variation Pathology Predictive Value of Tests Reproducibility of Results Time Factors Treatment Outcome Tumors Weiss criteria |
| title | Comparison of the methods for measuring the Ki-67 labeling index in adrenocortical carcinoma: manual versus digital image analysis |
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