{"title":"早期腔隙性乳腺癌的肿瘤增殖标志物分析:利用有丝分裂活动指数、Ki-67 和磷酸组蛋白 H3 表达的综合研究","authors":"P Jamshiya, Soundarya Ravi, Srinivas Bheemanathi Hanuman, Sree Rekha Jinkala, Ankit Jain, Prasanth Penumadu","doi":"10.1177/10668969241295355","DOIUrl":null,"url":null,"abstract":"<p><p><i>Introduction and Aim:</i> Routinely used proliferation markers such as mitotic activity index (MAI) and Ki-67 index show limited reproducibility due to high interobserver variability in breast cancer assessment. Phosphohistone H3 (PhH3), a novel proliferation marker, is gaining attention in breast cancer research. This study aimed to evaluate the inter-rater agreement among MAI, Ki-67, and PhH3 expressions in early-stage luminal breast cancer and assess the impact of replacing MAI with PhH3 index on tumor histological grading. <i>Materials and Methods:</i> Three pathologists assessed MAI, Ki-67, and PhH3 expressions in 66 early-stage luminal breast cancer specimens. Mitotic Activity Index was scored based on mitotic figures in an area of 2 mm<sup>2</sup> while Ki-67 index utilized a 14% threshold for positively stained nuclei. Phosphohistone H3 expression cutoff was set at 13 positive cells per 2 mm<sup>2</sup>. The inter-rater agreement for the 3 variables was analyzed using Cohen kappa statistics. <i>Results:</i> Among the 3 parameters, the kappa score of the PhH3 expression reflected very strong agreement between the 3 observers (κ = 0.991, 0.907, and 0.916). Only moderate agreement was noted for MAI (κ = 0.898, 0.562, and 0.592) and substantial agreement for Ki-67 index (κ = 0.869, 0.673, and 0.678). Moreover, replacing MAI with PhH3 index led to upgrade of histological grade in 15% to 16% of patients. <i>Conclusion:</i> Our study demonstrated that PhH3 is a more reproducible proliferation marker than MAI and Ki-67. Incorporation of PhH3-based mitotic index in breast cancer grading might reduce the variation in the assessment of histological grade.</p>","PeriodicalId":14416,"journal":{"name":"International Journal of Surgical Pathology","volume":" ","pages":"882-890"},"PeriodicalIF":1.0000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Analysis of Tumor Proliferation Markers in Early-Stage Luminal Breast Cancer: A Comprehensive Study Using Mitotic Activity Index, Ki-67, and Phosphohistone H3 Expression.\",\"authors\":\"P Jamshiya, Soundarya Ravi, Srinivas Bheemanathi Hanuman, Sree Rekha Jinkala, Ankit Jain, Prasanth Penumadu\",\"doi\":\"10.1177/10668969241295355\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Introduction and Aim:</i> Routinely used proliferation markers such as mitotic activity index (MAI) and Ki-67 index show limited reproducibility due to high interobserver variability in breast cancer assessment. Phosphohistone H3 (PhH3), a novel proliferation marker, is gaining attention in breast cancer research. This study aimed to evaluate the inter-rater agreement among MAI, Ki-67, and PhH3 expressions in early-stage luminal breast cancer and assess the impact of replacing MAI with PhH3 index on tumor histological grading. <i>Materials and Methods:</i> Three pathologists assessed MAI, Ki-67, and PhH3 expressions in 66 early-stage luminal breast cancer specimens. Mitotic Activity Index was scored based on mitotic figures in an area of 2 mm<sup>2</sup> while Ki-67 index utilized a 14% threshold for positively stained nuclei. Phosphohistone H3 expression cutoff was set at 13 positive cells per 2 mm<sup>2</sup>. The inter-rater agreement for the 3 variables was analyzed using Cohen kappa statistics. <i>Results:</i> Among the 3 parameters, the kappa score of the PhH3 expression reflected very strong agreement between the 3 observers (κ = 0.991, 0.907, and 0.916). Only moderate agreement was noted for MAI (κ = 0.898, 0.562, and 0.592) and substantial agreement for Ki-67 index (κ = 0.869, 0.673, and 0.678). Moreover, replacing MAI with PhH3 index led to upgrade of histological grade in 15% to 16% of patients. <i>Conclusion:</i> Our study demonstrated that PhH3 is a more reproducible proliferation marker than MAI and Ki-67. Incorporation of PhH3-based mitotic index in breast cancer grading might reduce the variation in the assessment of histological grade.</p>\",\"PeriodicalId\":14416,\"journal\":{\"name\":\"International Journal of Surgical Pathology\",\"volume\":\" \",\"pages\":\"882-890\"},\"PeriodicalIF\":1.0000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Surgical Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/10668969241295355\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Surgical Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/10668969241295355","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/15 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"PATHOLOGY","Score":null,"Total":0}
Analysis of Tumor Proliferation Markers in Early-Stage Luminal Breast Cancer: A Comprehensive Study Using Mitotic Activity Index, Ki-67, and Phosphohistone H3 Expression.
Introduction and Aim: Routinely used proliferation markers such as mitotic activity index (MAI) and Ki-67 index show limited reproducibility due to high interobserver variability in breast cancer assessment. Phosphohistone H3 (PhH3), a novel proliferation marker, is gaining attention in breast cancer research. This study aimed to evaluate the inter-rater agreement among MAI, Ki-67, and PhH3 expressions in early-stage luminal breast cancer and assess the impact of replacing MAI with PhH3 index on tumor histological grading. Materials and Methods: Three pathologists assessed MAI, Ki-67, and PhH3 expressions in 66 early-stage luminal breast cancer specimens. Mitotic Activity Index was scored based on mitotic figures in an area of 2 mm2 while Ki-67 index utilized a 14% threshold for positively stained nuclei. Phosphohistone H3 expression cutoff was set at 13 positive cells per 2 mm2. The inter-rater agreement for the 3 variables was analyzed using Cohen kappa statistics. Results: Among the 3 parameters, the kappa score of the PhH3 expression reflected very strong agreement between the 3 observers (κ = 0.991, 0.907, and 0.916). Only moderate agreement was noted for MAI (κ = 0.898, 0.562, and 0.592) and substantial agreement for Ki-67 index (κ = 0.869, 0.673, and 0.678). Moreover, replacing MAI with PhH3 index led to upgrade of histological grade in 15% to 16% of patients. Conclusion: Our study demonstrated that PhH3 is a more reproducible proliferation marker than MAI and Ki-67. Incorporation of PhH3-based mitotic index in breast cancer grading might reduce the variation in the assessment of histological grade.
期刊介绍:
International Journal of Surgical Pathology (IJSP) is a peer-reviewed journal published eight times a year, which offers original research and observations covering all major organ systems, timely reviews of new techniques and procedures, discussions of controversies in surgical pathology, case reports, and images in pathology. This journal is a member of the Committee on Publication Ethics (COPE).