The Biomarker Ki-67: Promise, Potential, and Problems in Breast Cancer.
Journal
Applied immunohistochemistry & molecular morphology : AIMM
ISSN: 1533-4058
Titre abrégé: Appl Immunohistochem Mol Morphol
Pays: United States
ID NLM: 100888796
Informations de publication
Date de publication:
01 08 2023
01 08 2023
Historique:
received:
15
10
2022
accepted:
19
10
2022
medline:
7
8
2023
pubmed:
3
2
2023
entrez:
2
2
2023
Statut:
ppublish
Résumé
Ki-67 is a nuclear protein serendipitously discovered by monoclonal antibody selection in the early 1980s. While it has been applied for decades in the context of breast cancer as a putative prognostic and, more recently, predictive, biomarker, even after all this time there is incomplete agreement as to the validity of the immunohistochemical assays employed for Ki-67 assessment, given possible effects of the disparate methodologies employed and possible confounding preanalytical, analytical, and interpretive variables. In this brief review, the history of Ki-67 and the problems, particularly with the analytical and interpretive variables, are highlighted through a selective review of the published literature. The contributions of the International Ki-67 Breast Cancer Working Group are highlighted, and in particular, the recommendations made by this group are reviewed. The potential of Ki-67 as a biomarker for breast cancer has not yet been fully realized, but an understanding of the power as well as the limitations of the methods of Ki-67 assessment are important if this biomarker can realize its potential.
Identifiants
pubmed: 36730064
doi: 10.1097/PAI.0000000000001087
pii: 00129039-990000000-00067
doi:
Substances chimiques
Ki-67 Antigen
0
Biomarkers, Tumor
0
Antibodies, Monoclonal
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
478-484Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Références
Gerdes J, Schwab U, Lemke H, et al. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13–20.
Shi SR, Chaiwun B, Young L, et al. Antigen retrieval technique utilizing citrate buffer or urea solution for immunohistochemical demonstration of androgen receptor in formalin-fixed paraffin sections. J Histochem Cytochem. 1993;41:1599–1604.
Gown AM, de Wever N, Battifora H. Microwave-based antigenic unmasking: a revolutionary new technique for routine immunohistochemistry. Appl Immunohistochem. 1993;1:256–266.
Cattoretti G, Becker MH, Key G, et al. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol. 1992;168:357–363.
Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–322.
Menon SS, Guruvayoorappan C, Sakthivel KM, et al. Ki-67 protein as a tumour proliferation marker. Clin Chim Acta. 2019;491:39–45.
Remnant L, Kochanova NY, Reid C, et al. The intrinsically disorderly story of Ki-67. Open Biol. 2021;11:210120.
Schluter C, Duchrow M, Wohlenberg C, et al. The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J Cell Biol. 1993;123:513–522.
Sun X, Kaufman PD. Ki-67: more than a proliferation marker. Chromosoma. 2018;127:175–186.
Sobecki M, Mrouj K, Camasses A, et al. The cell proliferation antigen Ki-67 organises heterochromatin. eLife. 2016;5:e13722.
Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984;133:1710–1715.
Gerdes J, Pickartz H, Brotherton J, et al. Growth fractions and estrogen receptors in human breast cancers as determined in situ with monoclonal antibodies. Am J Pathol. 1987;129:486–492.
de Azambuja E, Cardoso F, de Castro G Jr, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96:1504–1513.
Petrelli F, Viale G, Cabiddu M, et al. Prognostic value of different cut-off levels of Ki-67 in breast cancer: a systematic review and meta-analysis of 64,196 patients. Breast Cancer Res Treat. 2015;153:477–491.
Inwald EC, Klinkhammer-Schalke M, Hofstadter F, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 2013;139:539–552.
Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–2826.
Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11:55–65.
Sahebjam S, Aloyz R, Pilavdzic D, et al. Ki 67 is a major, but not the sole determinant of Oncotype Dx recurrence score. Br J Cancer. 2011;105:1342–1345.
Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726–3734.
Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111–121.
Viale G, Regan MM, Mastropasqua MG, et al. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst. 2008;100:207–212.
Viale G, Giobbie-Hurder A, Regan MM, et al. Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol. 2008;26:5569–5575.
Acs B, Zambo V, Vizkeleti L, et al. Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy. Diagn Pathol. 2017;12:20.
Kalvala J, Parks RM, Green AR, et al. Concordance between core needle biopsy and surgical excision specimens for Ki-67 in breast cancer—a systematic review of the literature. Histopathology. 2022;80:468–484.
Acs B, Leung SCY, Kidwell KM, et al. Systematically higher Ki-67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study. Mod Pathol. 2022;35:1362–1369.
Hitchman E, Hodgkinson C, Roberts D, et al. Effect of prolonged formalin fixation on immunohistochemical staining for the proliferation marker Ki67. Histopathology. 2011;59:1261–1263.
Arima N, Nishimura R, Osako T, et al. The importance of tissue handling of surgically removed breast cancer for an accurate assessment of the Ki-67 index. J Clin Pathol. 2016;69:255–259.
Kalkman S, Bulte JP, Halilovic A, et al. Brief fixation does not hamper the reliability of Ki67 analysis in breast cancer core-needle biopsies: a double-centre study. Histopathology. 2015;66:380–387.
Tang LH, Gonen M, Hedvat C, et al. Objective quantification of the Ki67 proliferative index in neuroendocrine tumors of the gastroenteropancreatic system: a comparison of digital image analysis with manual methods. Am J Surg Pathol. 2012;36:1761–1770.
van den Berg EJ, Duarte R, Dickens C, et al. Ki67 immunohistochemistry quantification in breast carcinoma: a comparison of visual estimation, counting, and ImmunoRatio. Appl Immunohistochem Mol Morphol. 2021;29:105–111.
Reid MD, Bagci P, Ohike N, et al. Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies. Mod Pathol. 2015;28:686–694.
Polley MY, Leung SC, McShane LM, et al. An International Ki67 Reproducibility Study. J Natl Cancer Inst. 2013;105:1897–1906.
Polley MY, Leung SC, Gao D, et al. An international study to increase concordance in Ki67 scoring. Mod Pathol. 2015;28:778–786.
Leung SCY, Nielsen TO, Zabaglo L, et al. Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration. NPJ Breast Cancer. 2016;2:16014.
Leung SCY, Nielsen TO, Zabaglo LA, et al. Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration. Histopathology. 2019;75:225–235.
Acs B, Rantalainen M, Hartman J. Artificial intelligence as the next step towards precision pathology. J Intern Med. 2020;288:62–81.
Jahn SW, Plass M, Moinfar F. Digital pathology: advantages, limitations and emerging perspectives. J Clin Med. 2020;9:3697.
Stenzinger A, Alber M, Allgauer M, et al. Artificial intelligence and pathology: from principles to practice and future applications in histomorphology and molecular profiling. Semin Cancer Biol. 2022;84:129–143.
Fitzgerald J, Higgins D, Mazo Vargas C, et al. Future of biomarker evaluation in the realm of artificial intelligence algorithms: application in improved therapeutic stratification of patients with breast and prostate cancer. J Clin Pathol. 2021;74:429–434.
Dawson H. Digital pathology—rising to the challenge. Front Med (Lausanne). 2022;9:888896.
Rimm DL, Leung SCY, McShane LM, et al. An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer. Mod Pathol. 2019;32:59–69.
Acs B, Pelekanou V, Bai Y, et al. Ki67 reproducibility using digital image analysis: an inter-platform and inter-operator study. Lab Invest. 2019;99:107–117.
Nielsen TO, Leung SCY, Rimm DL, et al. Assessment of Ki67 in breast cancer: updated recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst. 2021;113:808–819.
Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Arch Pathol Lab Med. 2018;142:1364–1382.
Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update. Arch Pathol Lab Med. 2020;144:545–563.
Laenkholm AV, Grabau D, Moller Talman ML, et al. An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish Breast Cancer Cooperative Group (DBCG). Acta Oncol. 2018;57:83–89.
Gnant M, Harbeck N, Thomssen C. St. Gallen 2011: Summary of the Consensus Discussion. Breast Care (Basel). 2011;6:136–141.
Aung TN, Acs B, Warrell J, et al. A new tool for technical standardization of the Ki-67 immunohistochemical assay. Mod Pathol. 2021;34:1261–1270.
Royce M, Osgood C, Mulkey F, et al. FDA approval summary: abemaciclib with endocrine therapy for high-risk early breast cancer. J Clin Oncol. 2022;40:1155–1162.
Dowsett M, Nielsen TO, Rimm DL, et al. Ki-67 as a companion diagnostic: good or bad news? J Clin Oncol. 2022;40:3796–99.