{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:55:54Z","timestamp":1791352554615,"version":"4.3.1"},"reference-count":84,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"abstract":"<jats:p>Ki\u201067 is a well\u2010established marker of tumour proliferation and an important prognostic and predictive biomarker in breast cancer, particularly in hormone receptor\u2013positive (HR\u2010positive), HER2\u2010negative disease. Despite its biological relevance, clinical implementation has been limited by the reported interobserver and interlaboratory variability. Recent therapeutic advances have created an increased need for accurate and reproducible Ki\u201067 assessment in clinical practice. This review summarizes the biological basis for the use of Ki\u201067 as a marker of proliferation, technical requirements for reliable immunohistochemistry and the influence of pre\u2010analytical and analytical variables on staining performance. We evaluate established and emerging scoring approaches and provide scoring recommendations for practising pathologists. A simplified calibrated global assessment method is presented as an alternative to exhaustive visual quantification that preserves its accuracy while substantially reducing scoring time and avoiding the variability of estimated methods. Image analysis\/artificial intelligence (AI) using validated algorithms is recommended where available. We also review the role of Ki\u201067 in predicting response to neoadjuvant endocrine and chemotherapy, its integration into prognostic models such as the PEPI score, and its utility in selecting patients for adjuvant CDK4\/6 inhibition. The limitations of fixed cut\u2010off values are discussed, together with the potential advantages of tiered classification and continuous modelling. Finally, we outline the growing role of digital pathology and AI, which have demonstrated improved reproducibility, reduced turnaround time, and prognostic performance superior to manual scoring. Ki\u201067 is a clinically meaningful biomarker, the value of which can only be fully realized through rigorous standardization, validated scoring approaches and close communication between pathologists and oncologists. This guidance provides a practical framework for high\u2010quality Ki\u201067 assessment and supports its safe and effective integration into contemporary breast cancer management.<\/jats:p>","DOI":"10.1111\/his.70235","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T08:34:33Z","timestamp":1784363673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>UK<\/scp>\n                    recommendations for Ki\u201067 immunohistochemical staining and interpretation in breast cancer"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5784-8705","authenticated-orcid":false,"given":"Abeer M","family":"Shaaban","sequence":"first","affiliation":[{"name":"Cancer and Genomic Sciences University of Birmingham  Birmingham UK"},{"name":"Cellular Pathology Queen Elizabeth Hospital Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-2362","authenticated-orcid":false,"given":"Andrew","family":"Dodson","sequence":"additional","affiliation":[{"name":"UK National External Quality Assessment Scheme for Immunohistochemistry and In Situ Hybridisation  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-5525","authenticated-orcid":false,"given":"Emad","family":"Rakha","sequence":"additional","affiliation":[{"name":"Academic Unit for Translational Medical Sciences, School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5292-8474","authenticated-orcid":false,"given":"Ian","family":"Ellis","sequence":"additional","affiliation":[{"name":"Department of Histopathology, City Hospital Campus Nottingham University Hospitals  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7301-4030","authenticated-orcid":false,"given":"Daniel","family":"Rea","sequence":"additional","affiliation":[{"name":"Cancer Research United Kingdom Clinical Trials Unit at University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8920-5480","authenticated-orcid":false,"given":"Cecily","family":"Quinn","sequence":"additional","affiliation":[{"name":"Irish National Breast Screening Programme and Department of Histopathology St. Vincent's University Hospital  Dublin Ireland"},{"name":"School of Medicine University College  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3345-3965","authenticated-orcid":false,"given":"Elena","family":"Provenzano","sequence":"additional","affiliation":[{"name":"Addenbrookes Hospital and NIHR Cambridge Biomedical Research Centre  Cambridge UK"},{"name":"Department of Histopathology Cambridge University NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4167-8910","authenticated-orcid":false,"given":"Sarah","family":"Pinder","sequence":"additional","affiliation":[{"name":"School of Cancer and Pharmaceutical Sciences King's College  London UK"},{"name":"Guy's and St Thomas' Hospitals  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the UK National Coordinating Committee for Breast Pathology (NCCBP), Association of Breast Pathology (ABP) and the UK National External Quality Assessment Scheme for Immunohistochemistry and In Situ Hybridisation (UK NEQAS ICC & ISH)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"e_1_2_14_2_1","unstructured":"National Institute for Health and Care Excellence.Ribociclib with an aromatase inhibitor for adjuvant treatment of hormone receptor\u2010positive HER2\u2010negative early breast cancer at high risk of recurrence technology appraisal guidance. 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