Affinage

MKI67

Proliferation marker protein Ki-67 · UniProt P46013

Round 2 corrected
Length
3256 aa
Mass
358.7 kDa
Annotated
2026-04-28
130 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Ki-67 (MKI67) is a large, intrinsically disordered nuclear nonhistone protein that functions as a multivalent organizer of chromosome surface architecture and nuclear compartmentalization during the cell cycle. During mitosis, Ki-67 forms a dense surfactant-like brush on the perichromosomal layer that prevents chromosome aggregation through steric and electrostatic repulsion, then collapses into an adhesive state at anaphase to cluster chromosomes and exclude cytoplasmic ribosomes from the reforming nucleus (PMID:27362226, PMID:32879492). During interphase, Ki-67 localizes to nucleoli and rRNA gene chromatin, where it organizes heterochromatin spatial distribution, competes with the nuclear lamina for late-replicating genomic domains, controls pericentromeric replication timing, and is required at replication forks for fork protection and genome stability through a HUWE1/cGAS-STING-linked pathway (PMID:16206250, PMID:26949251, PMID:36245428, PMID:38649976). Ki-67 recruits protein phosphatase 1 (PP1) to chromatin at anaphase onset via a structurally defined interface regulated by Aurora B kinase, and despite its universal use as a proliferation marker, Ki-67-null mice are viable and Ki-67-depleted cells proliferate, establishing that it is dispensable for cell division per se (PMID:27572260, PMID:26949251).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1991 High

    Establishing the molecular identity of the Ki-67 antigen resolved whether this widely used proliferation marker was a histone or a novel protein: it proved to be a nonhistone nuclear protein of ~395/345 kDa expressed exclusively in cycling cells, and antisense inhibition suggested a functional requirement for proliferation.

    Evidence Immunoblot, enzymatic digestion, molecular cloning, and antisense oligonucleotide inhibition in IM-9 cells

    PMID:2012175

    Open questions at the time
    • Antisense approach does not distinguish direct from indirect effects on proliferation
    • No loss-of-function genetics performed
  2. 1993 High

    Full-length cDNA cloning revealed the domain architecture of Ki-67, identifying 16 tandem 366-bp repeats containing a conserved 66-bp motif as the antibody epitope, and establishing that the protein has no homology to any known protein family.

    Evidence cDNA cloning and sequencing, Northern blot, bacterial expression, immunoblot

    PMID:8227122

    Open questions at the time
    • No structural information on the repeat region
    • Functional significance of the repeats undefined
  3. 2006 High

    Demonstrating that Ki-67 associates with rRNA gene chromatin via ChIP established its first direct chromatin target, linking it to ribosomal RNA transcription rather than generic chromosome packaging.

    Evidence ChIP at rRNA promoter and transcribed regions, immunofluorescence colocalization with rRNA transcription sites

    PMID:16206250

    Open questions at the time
    • Whether Ki-67 directly regulates rRNA transcription rates was not tested
    • Mechanism of recruitment to rDNA undefined
  4. 2016 High

    Three landmark studies collectively redefined Ki-67 function: it acts as a biophysical surfactant on mitotic chromosomes preventing aggregation through size and charge rather than a specific domain; it recruits PP1 to chromatin at anaphase via a structurally resolved interface regulated by Aurora B; and mouse knockout showed it is dispensable for proliferation but required for heterochromatin spatial organization, resolving the long-standing paradox of its use as a proliferation marker.

    Evidence Fluorescence correlation spectroscopy and truncation mutants (surfactant); X-ray crystallography and biochemical reconstitution (PP1); mouse knockout with Hi-C, interactome, and heterochromatin imaging (dispensability and heterochromatin role)

    PMID:26949251 PMID:27362226 PMID:27572260

    Open questions at the time
    • Structural basis of the surfactant-to-adhesive transition unresolved
    • Which PP1 substrates are relevant at mitotic exit not identified
    • How heterochromatin misorganization affects long-term fitness unclear
  5. 2020 High

    The discovery that Ki-67 switches from a repulsive brush to an adhesive state at anaphase, clustering chromosomes to exclude ribosomes from the reforming nucleus, established a direct mechanism for nuclear-cytoplasmic compartmentalization after open mitosis.

    Evidence Live-cell imaging in HeLa cells, Ki-67 depletion, ribosome reporter exclusion assay

    PMID:32879492

    Open questions at the time
    • Molecular trigger for the repulsive-to-adhesive switch not defined
    • Whether other perichromosomal proteins contribute redundantly to ribosome exclusion not resolved
  6. 2022 High

    Genome-wide proximity mapping showed Ki-67 associates with late-replicating domains throughout the cell cycle and competes with the nuclear lamina for these genomic regions, establishing a role in replication timing control of pericentromeric regions.

    Evidence pA-DamID in human cell lines, nucleolar perturbation, replication timing assays

    PMID:36245428

    Open questions at the time
    • Mechanism by which Ki-67 antagonizes lamina contacts not defined
    • Whether replication timing changes have phenotypic consequences unclear
  7. 2023 Medium

    Identification of CCDC86 as a Ki-67-interacting protein in the perichromosomal layer expanded the molecular inventory of the chromosome periphery and showed CCDC86 depletion disorganizes Ki-67 and nucleolin localization during mitosis.

    Evidence Co-immunoprecipitation, RNAi depletion, fluorescence microscopy

    PMID:36695333

    Open questions at the time
    • Whether CCDC86 directly binds Ki-67 or requires bridging partners not determined
    • Reciprocal dependency (Ki-67 depletion effect on CCDC86) not fully tested
  8. 2024 High

    Acute depletion revealed a direct S-phase function: Ki-67 is required for replication fork stability, and its loss causes replication machinery unloading, HUWE1-dependent undetected DNA damage, cohesion defects, and cGAS/STING-mediated interferon activation, uncoupling Ki-67 function from its mitotic roles.

    Evidence Inducible degron-mediated acute Ki-67 degradation in HCT116 cells, APEX2 proximity proteomics, DNA fiber assays, cGAS/STING pathway analysis

    PMID:38649976

    Open questions at the time
    • Direct molecular targets of Ki-67 at forks not identified
    • Whether replication fork protection depends on Ki-67's PP1-recruiting activity untested
    • Connection between cohesion defects and cGAS activation not mechanistically resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the molecular trigger for Ki-67's repulsive-to-adhesive conformational switch at anaphase, identification of the PP1 substrates relevant to mitotic exit, and the structural basis by which an intrinsically disordered protein organizes heterochromatin domains genome-wide.
  • No atomic-resolution structure of full-length Ki-67 or its repeat region
  • Relative contribution of surfactant versus PP1-scaffold versus heterochromatin-organizer functions to cellular fitness undefined
  • Whether Ki-67's replication fork role and its heterochromatin-organizing role are mechanistically linked is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 1 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 4 GO:0005730 nucleolus 3
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-4839726 Chromatin organization 2 R-HSA-69306 DNA Replication 2
Partners
CCDC86HUWE1NCLNPM1PPP1CAPPP1CBSP1
Complex memberships
Ki-67–PP1 holoenzymePerichromosomal layer (PCL)

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Ki-67 antigen was identified as a nonhistone nuclear protein forming a double band at ~395 kDa and ~345 kDa, expressed exclusively in proliferating cells but absent in quiescent cells. Antisense oligonucleotides against Ki-67 antigen inhibited proliferation of IM-9 cells, indicating Ki-67 may be an absolute requirement for maintaining cell proliferation. Immunoblot, enzymatic digestion, molecular cloning from lambda gt11 library, antisense oligonucleotide inhibition The American journal of pathology High 2012175
1993 Full-length cDNA cloning revealed that Ki-67 antigen is encoded by two differentially spliced mRNA isoforms (9,768 bp and 8,688 bp ORFs), encoding proteins of ~358 kDa and ~319 kDa. The central region contains 16 tandemly repeated 366-bp elements ('Ki-67 repeats'), each with a conserved 66-bp 'Ki-67 motif' that encodes the epitope recognized by Ki-67 antibody. The protein has no homology to known sequences and represents a new category of cell cycle-associated nuclear nonhistone proteins. Full-length cDNA cloning and sequencing, Northern blot, bacterial expression, immunoblot with novel mAbs The Journal of cell biology High 8227122
2000 Ki-67 protein undergoes phosphorylation by cdc2 kinase and PKC, and these posttranslational modifications accompany redistribution from the nuclear interior to the perichromosomal layer during mitosis and back during mitotic exit. Review summarizing phosphorylation evidence and relocalization data Experimental cell research Medium 10837136
2006 Ki-67 protein (pKi-67) is physically associated with ribosomal RNA transcription machinery in both quiescent and proliferating cells. ChIP assays showed pKi-67 associates with chromatin of the rRNA gene promoter and transcribed region, and a fraction of pKi-67 localizes to sites linked to rRNA synthesis during interphase and mitosis. Chromatin immunoprecipitation (ChIP), immunofluorescence with novel antibody TuBB-9, colocalization with rRNA transcription sites Journal of cellular physiology High 16206250
2016 Ki-67 acts as a biological surfactant on the mitotic chromosome surface to prevent chromosomes from aggregating into a single chromatin mass after nuclear envelope disassembly, enabling independent chromosome motility and efficient spindle interactions. Ki-67 forms a high-density surface brush at the chromosome periphery in an extended molecular conformation. The surfactant function correlates with size and net charge of the protein rather than a specific domain, suggesting a steric and electrostatic charge barrier mechanism. Fluorescence correlation spectroscopy, dual-colour labelling of protein termini, truncation mutant analysis, live-cell imaging of chromosome individualization after Ki-67 depletion Nature High 27362226
2016 Ki-67 controls heterochromatin organisation. Ki-67 depletion disrupts nucleologenesis, alters gene expression, disrupts heterochromatin compaction and long-range genomic interactions, and relocalizes H3K9me3 and H4K20me3. Overexpression of human or Xenopus Ki-67 induces ectopic heterochromatin formation. Ki-67 interactors include nucleolar process proteins and chromatin regulators. Ki-67 mutant mice are viable and cells lacking Ki-67 proliferate efficiently, demonstrating Ki-67 is dispensable for proliferation but required for heterochromatin spatial organisation. Mouse knockout, Ki-67 overexpression in differentiated tissues, Co-IP/interactome, Hi-C chromatin interaction mapping, H3K9me3/H4K20me3 immunostaining, nucleologenesis assay, gene expression profiling eLife High 26949251
2016 Ki-67 and RepoMan recruit protein phosphatase 1 (PP1) to chromatin at anaphase onset using an identical yet novel mechanism, binding a PP1 pocket engaged only by these two regulators. Ki-67 and RepoMan distinguish between distinct PP1 isoforms. Assembly of these holoenzymes is dynamically regulated by Aurora B kinase phosphorylation during mitosis. This defines Ki-67 as a scaffold for a mitotic exit phosphatase. Structural biology (X-ray crystallography), biochemical reconstitution, mutagenesis, in vitro binding assays, mass spectrometry, cell biology eLife High 27572260
2004 During early mouse development, Ki-67 protein shows sex-specific expression: it is present in MII oocytes but absent in mature sperm. After fertilization, both pronuclei show little or no Ki-67 until prophase of the first mitosis, when chromosomes of both pronuclei are simultaneously decorated with Ki-67. In 2-cell embryos, Ki-67 localizes preferentially to nucleolus precursor bodies (NPBs). From the 4-cell stage onwards, Ki-67 shows the regular cell-cycle-dependent nuclear relocalization pattern: perichromosomal layer during mitosis, distributed in whole nucleus in early G1, and associated with NPBs/nucleolus for the rest of the cell cycle. Immunofluorescence microscopy in mouse embryos at successive developmental stages Cytogenetic and genome research Medium 15237214
2020 During mitotic exit, Ki-67 promotes chromosome clustering at the anaphase spindle poles by collapsing from repulsive molecular brushes to an adhesive state. This Ki-67-mediated chromosome clustering excludes large cytoplasmic components (including mature ribosomes) from the nucleus as the nuclear envelope reforms, re-establishing nuclear/cytoplasmic compartmentalization after open mitosis. Exclusion of ribosomes from the reforming nucleus depends on Ki-67-regulated chromosome clustering. Live-cell imaging in HeLa cells, Ki-67 depletion, ribosome reporter exclusion assay, microtubule-independent mechanism demonstrated Nature High 32879492
2022 Ki-67 associates with large late-replicating genomic domains throughout the cell cycle. Early in interphase Ki-67 (in pre-nucleolar bodies) interacts with these domains on all chromosomes; later in interphase, when Ki-67 is confined to nucleoli, it shifts toward small chromosomes. Ki-67 does not detectably control chromatin-chromatin interactions during interphase but competes with the nuclear lamina for interaction with late-replicating DNA and controls replication timing of (peri)centromeric regions. pA-DamID genomic mapping in human cell lines, nucleolar perturbation experiments, replication timing assay EMBO reports High 36245428
2024 Ki-67 plays a role during DNA replication: acute depletion causes severely delayed DNA replication, unloading of the replication machinery, DNA damage not sensed by canonical pathways (dependent on HUWE1 ligase), defects in sister chromatid cohesion, and activation of an interferon response via the cGAS/STING pathway. APEX2 proteomics identified novel Ki-67 interactors at replication forks. Doxycycline-inducible E3 ligase plus auxin-inducible degron (AID) system for rapid Ki-67 degradation in HCT116 cells, APEX2 proximity proteomics, phospho-proteomics, DNA fiber assay, cGAS/STING pathway analysis Genome biology High 38649976
2012 IRF1 represses Ki-67 gene transcription in a dose-dependent manner in renal carcinoma cells. The Ki-67 core promoter contains two functional Sp1 binding sites required for its activity; IRF1 decreases endogenous Sp1 protein levels (without affecting Sp1 mRNA), thereby suppressing Ki-67 promoter activity through interference with Sp1-dependent activation. Promoter reporter assays, site-directed mutagenesis of Sp1 sites, IRF1 overexpression, Western blot and RT-PCR for Sp1 levels Tumour biology Medium 22890831
2023 CCDC86 (cyclon) is a novel Ki-67-interacting protein in the chromosome periphery. CCDC86 depletion by RNAi causes partial disorganisation of the chromosome periphery with altered Ki-67 and nucleolin localisation, formation of abnormal cytoplasmic aggregates, chromosome alignment errors, altered spindle length, and increased apoptosis. CCDC86 is part of subcomplexes with nucleolin and B23/NPM1 required for spindle regulation and kinetochore-microtubule attachments. RNAi depletion, co-immunoprecipitation, fluorescence microscopy, biochemical fractionation Journal of cell science Medium 36695333
2016 Ki-67 protein is required for normal nucleolar association of heterochromatin during interphase and for formation of the perichromosomal layer (PCL), a ribonucleoprotein sheath coating condensed chromosomes during mitosis. Within the PCL, Ki-67 prevents aggregation of mitotic chromosomes. Review synthesizing functional studies including depletion experiments and localization studies (summarized mechanistic findings) Chromosoma Medium 29322240

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The Ki-67 protein: from the known and the unknown. Journal of cellular physiology 3486 10653597
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. The Journal of cell biology 1850 22412018
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2009 Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. Journal of the National Cancer Institute 1642 19436038
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 909 24356306
1991 Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. The American journal of pathology 840 2012175
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2005 Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. The Journal of clinical investigation 760 15931389
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2018 Ki-67: more than a proliferation marker. Chromosoma 672 29322240
1993 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. The Journal of cell biology 670 8227122
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2002 The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis. Journal of neuroscience methods 649 11897369
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2013 Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast cancer research and treatment 424 23674192
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2016 Ki-67 acts as a biological surfactant to disperse mitotic chromosomes. Nature 414 27362226
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2019 Ki-67 protein as a tumour proliferation marker. Clinica chimica acta; international journal of clinical chemistry 348 30653951
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2000 The Ki-67 protein: fascinating forms and an unknown function. Experimental cell research 311 10837136
2006 Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. Journal of cellular physiology 306 16206250
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 263 26949251
1987 Proliferative potential of meningiomas determined with the monoclonal antibody Ki-67. Acta neuropathologica 122 3618128
1998 Positivity of the proliferation marker Ki-67 in noncycling cells. American journal of clinical pathology 120 9661919
2003 The Ki-67 proliferation antigen in meningiomas. Experience in 600 cases. Acta neurochirurgica 102 14740263
1995 A clinicopathologic study of 233 cases with special reference to evaluation with the MIB-1 index. Cancer 100 8620403
1991 Ki-67 immunostaining and survival in operable lung cancer. Histopathology 97 1664810
2022 Physiological functions and roles in cancer of the proliferation marker Ki-67. Journal of cell science 82 35674256
1995 Use of the MIB-1 antibody for detecting proliferating cells in the retina. Investigative ophthalmology & visual science 80 7890504
1995 Clinical relevance of Ki-67 expression in bone tumors. Cancer 79 7828130
2021 The intrinsically disorderly story of Ki-67. Open biology 76 34375547
2001 Immunohistochemical evaluation of PCNA and Ki-67 in ameloblastoma. Oral oncology 75 11167148
2020 Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly. Nature 74 32879492
2000 Predictive value of p53, mdm-2, p21, and mib-1 for chemotherapy response in advanced breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 73 10955790
1998 MIB-1 labeling indices in benign, aggressive, and malignant meningiomas: a study of 90 tumors. Human pathology 73 9865827
2017 MCM2: An alternative to Ki-67 for measuring breast cancer cell proliferation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 61 28084344
1998 The relationship between MIB-1 proliferation index and outcome in pancreatic neuroendocrine tumors. American journal of clinical pathology 60 9495200
2017 Ki-67 and the Chromosome Periphery Compartment in Mitosis. Trends in cell biology 59 28838621
2012 Phenotyping of pulmonary carcinoids and a Ki-67-based grading approach. Virchows Archiv : an international journal of pathology 59 22293945
2011 Evaluation of cervical cone biopsies for coexpression of p16INK4a and Ki-67 in epithelial cells. International journal of cancer 58 21387293
2003 P53 and MIB-1 immunohistochemistry as predictors of the clinical behavior of nonfunctioning pituitary adenomas. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 58 12945944
1996 Gastric fundic gland polyps: a morphological study including mucin histochemistry, stereometry, and MIB-1 immunohistochemistry. Human pathology 57 8816883
2016 The Ki-67 and RepoMan mitotic phosphatases assemble via an identical, yet novel mechanism. eLife 54 27572260
2019 Ki-67/MKI67 as a Predictive Biomarker for Clinical Outcome in Gastric Cancer Patients: an Updated Meta-analysis and Systematic Review involving 53 Studies and 7078 Patients. Journal of Cancer 46 31632479
2005 Utility of cytokeratin 20 and Ki-67 as markers of urothelial dysplasia. Pathology international 46 15871722
2018 Comparison of central laboratory assessments of ER, PR, HER2, and Ki67 by IHC/FISH and the corresponding mRNAs (ESR1, PGR, ERBB2, and MKi67) by RT-qPCR on an automated, broadly deployed diagnostic platform. Breast cancer research and treatment 44 30120700
1997 No prediction of recurrence of meningiomas by PCNA and Ki-67 immunohistochemistry. Journal of neuro-oncology 41 9258816
2002 Evaluation of MIB-1-positive cell clusters as a diagnostic marker for cervical intraepithelial neoplasia. The American journal of surgical pathology 37 12409727
2007 Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies. Annals of the rheumatic diseases 36 17613556
2006 Celecoxib decreases Ki-67 proliferative index in active smokers. Clinical cancer research : an official journal of the American Association for Cancer Research 35 16397057
2022 Lung carcinoid tumours: histology and Ki-67, the eternal rivalry. Histopathology 34 36239545
2017 An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®. Breast cancer research : BCR 34 28490348
1998 Cell proliferation rate by MIB-1 immunohistochemistry predicts postradiation recurrence in prostatic adenocarcinomas. American journal of clinical pathology 34 9583887
1997 Comparison of quantitative and semiquantitative methods of assessing MIB-1 with the S-phase fraction in breast carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 34 9267818
2008 p16, cyclin D1, Ki-67, and AMACR as markers for dysplasia in Barrett esophagus. Applied immunohistochemistry & molecular morphology : AIMM 33 18665038
1997 Myxopapillary ependymomas: a clinicopathologic study of 14 cases including MIB-1 and p53 immunoreactivity. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 31 9110291
2018 Expression and significance of Ki-67 in lung cancer. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 30 29940632
2017 Parafibromin, APC, and MIB-1 Are Useful Markers for Distinguishing Parathyroid Carcinomas From Adenomas. Applied immunohistochemistry & molecular morphology : AIMM 30 27490759
2016 Interobserver Variability of Ki-67 Measurement in Breast Cancer. Journal of pathology and translational medicine 30 26875758
2000 Endocervical intraepithelial glandular atypia (dysplasia): a histopathologic, human papillomavirus, and MIB-1 analysis of 25 cases. Human pathology 29 10872657
1999 Utility of proliferation-associated marker MIB-1 in evaluating lesions of the uterine cervix. Advances in anatomic pathology 28 10410171
2019 An oncogenic gene, SNRPA1, regulates PIK3R1, VEGFC, MKI67, CDK1 and other genes in colorectal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 31203132
2005 Correlation between choline and MIB-1 index in human gliomas. A quantitative in proton MR spectroscopy study. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 27 15925772
2024 Ki-67 is necessary during DNA replication for fork protection and genome stability. Genome biology 26 38649976
2017 Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 28700999
2000 Intracranial meningeal tumours in childhood: a clinicopathologic study including MIB-1 immunohistochemistry. Pathology, research and practice 26 10729919
1996 Proliferation index determined by MIB-1 and recurrence in endometrial cancer. Gynecologic oncology 26 8641618
2006 Mcm-2 and Ki-67 have limited potential in preoperative diagnosis of thyroid malignancy. The Laryngoscope 23 16885749
2001 Telomerase activity, MIB-1, PCNA, HPV 16 and p53 as diagnostic markers for cervical intraepithelial neoplasia. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 23 11878714
2017 Application of DWIBS in malignant lymphoma: correlation between ADC values and Ki-67 index. European radiology 22 29143105
1998 Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: a study of 48 cases. Human pathology 22 9865840
2009 Impact of morphology, MIB-1, p53 and MGMT on outcome in pilocytic astrocytomas. Brain pathology (Zurich, Switzerland) 21 19832838
2004 Expression of the proliferation marker Ki-67 during early mouse development. Cytogenetic and genome research 20 15237214
2007 Histological grading and MIB-1 labeling index of soft-tissue sarcomas. Pathology international 19 17295643
2004 Efficacy of rituximab plus chemotherapy in follicular lymphoma depends on Ki-67 expression. Pathology international 19 15363034
1997 Immunoreactivity to MIB-1 in breast cancer: methodological assessment and comparison with other proliferation indices. Cell proliferation 19 9375023
2022 Dynamic chromosomal interactions and control of heterochromatin positioning by Ki-67. EMBO reports 18 36245428
2013 Identifying Ki-67 specific miRNA-mRNA interactions in malignant astrocytomas. Neuroscience letters 18 23643983
2012 Immunohistochemical study of osteopontin, Ki-67, and CD34 of psoriasis in Mansoura, Egypt. Indian journal of pathology & microbiology 18 22499302
2016 The role of Ki-67 in breast cancer. South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie 17 28240498
2007 Utility of SKP2 and MIB-1 in grading follicular lymphoma using quantitative imaging analysis. Human pathology 17 17350668
1993 Restricted expression of Ki-67 in cholesteatoma epithelium. Archives of otolaryngology--head & neck surgery 17 7684591
2021 ESR1, PGR, ERBB2, and MKi67 mRNA expression in postmenopausal women with hormone receptor-positive early breast cancer: results from ABCSG Trial 6. ESMO open 15 34371382
2020 STMN1 and MKI67 Are Upregulated in Uterine Leiomyosarcoma and Are Potential Biomarkers for its Diagnosis. Medical science monitor : international medical journal of experimental and clinical research 15 32425177
2017 Predictive value of molecular subtyping in NMIBC by RT-qPCR of ERBB2, ESR1, PGR and MKI67 from formalin fixed TUR biopsies. Oncotarget 15 28978063
2022 The Biomarker Ki-67: Promise, Potential, and Problems in Breast Cancer. Applied immunohistochemistry & molecular morphology : AIMM 14 36730064
2013 Immunohistochemical detection of Hsp90 and Ki-67 in pterygium. Diagnostic pathology 14 23432803
1999 MIB-1 immunoreactivity correlates with blood vessel density and survival in disseminated malignant melanoma. Oncology 14 10545794
2014 Characterizing invading glioma cells based on IDH1-R132H and Ki-67 immunofluorescence. Brain tumor pathology 13 24384677
1990 Assessment of tumor cell kinetics by monoclonal antibody Ki-67. European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 13 2079097
2023 The Expression of Testin, Ki-67 and p16 in Cervical Cancer Diagnostics. Current issues in molecular biology 12 36661518
2021 FORGE: A Novel Scoring System to Predict the MIB-1 Labeling Index in Intracranial Meningiomas. Cancers 12 34298854
2002 bcl-2 and MIB-1 labeling indexes in cats with lymphoma. Journal of veterinary internal medicine 12 12465771
1997 Tumor cell counting using an image analysis program for MIB-1 immunohistochemistry. Neurologia medico-chirurgica 12 9059038
1993 PCNA independence of Ki-67 expression in HPV infection. Cell biology international 12 7906585
2021 Chromosome clustering in mitosis by the nuclear protein Ki-67. Biochemical Society transactions 11 34783345
2017 Role of p53 and Ki-67 immunomarkers in carcinoma of urinary bladder. Indian journal of pathology & microbiology 11 29323062
2010 Reinke's edema: investigations on the role of MIB-1 and hepatocyte growth factor. European journal of histochemistry : EJH 11 20819770
2003 Proliferative, infiltrative, and metastatic activities in colorectal tumors assessed by MIB-1 antibody. Oncology reports 11 14534689
2018 ki-67 and Topoisomerase IIa proliferation markers in colon adenocarcinoma. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 10 30722108
2016 Ki-67 is overexpressed in human laryngeal carcinoma and contributes to the proliferation of HEp2 cells. Oncology letters 10 27703526
2012 Immunohistochemical evaluation of p53 and Ki-67 proteins in colorectal adenomas. Arquivos de gastroenterologia 10 22481684
2012 IRF1 suppresses Ki-67 promoter activity through interfering with Sp1 activation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 22890831
2002 The course of MIB-1 expression by cerebral macrophages following human brain injury. Legal medicine (Tokyo, Japan) 10 12935673
1989 Effects of serum deprivation on Ki-67-reactive antigen. Expression in HeLa cells. Acta pathologica japonica 10 2589078
2014 Cytological Ki-67 in pancreatic endocrine tumors: a new "must"? Gland surgery 9 25493251
2010 Human gallbladder carcinoma: Role of neurotrophins, MIB-1, CD34 and CA15-3. European journal of histochemistry : EJH 9 20353905
2001 Clinicopathologic study of retinoblastoma including MIB-1, p53, and CD99 immunohistochemistry. Annals of diagnostic pathology 9 11436168
2000 bcl-2, p53, and MIB-1 in human adult dental pulp. Journal of endodontics 9 11199723
2023 CCDC86 is a novel Ki-67-interacting protein important for cell division. Journal of cell science 8 36695333
2022 Double Ki-67 and synaptophysin labeling in pancreatic neuroendocrine tumor biopsies. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 8 35292233
2022 MKI67 as a potential diagnostic biomarker in pulmonary hypertension. Frontiers in pediatrics 8 36389368
2021 Hepatoma upregulated protein and Ki-67 expression in resectable hepatocellular carcinoma. Journal of the Chinese Medical Association : JCMA 8 33883465
2011 A cytohistological study of Ki-67 expression in ovarian tumors. Indian journal of pathology & microbiology 8 21393871
2007 MIB-1, Bcl-2 and p53 in odontogenic myxomas of the jaws. Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale 8 18198753
1995 Vesical urothelium proliferation in spinal cord injured persons: an immunohistochemical study of PCNA and MIB.1 labelling. Paraplegia 8 8524605