MKI67

Overview

MKI67 (marker of proliferation Ki-67) is a nuclear protein expressed exclusively in proliferating cells (G1, S, G2, and M phases) and is the most widely used histological and flow-cytometric marker of cell proliferation. In cancer biology, MKI67/Ki-67 quantifies the proliferative fraction and is a prognostic marker across multiple tumor types.

Alterations observed in the corpus

  • MKI67 (Ki-67) IHC in grade II oligodendroglioma confirmed that proliferating cells are rare (1.5–8% of total cells) and are enriched in the stem/progenitor (SOX2/SOX4/SOX11-high) compartment rather than in differentiated oligo-like or astrocyte-like cells, validating the scRNA-seq developmental hierarchy PMID:27806376.
  • MKI67 is expressed in the proliferating hC1 progenitor cluster of postnatal human adrenal gland (alongside ASPM, BUB1), consistent with an active cell-cycling state in this novel progenitor population PMID:34493726.
  • In HNSCC reirradiation plus nivolumab, MKI67 (Ki-67) co-expression with PD-1 on peripheral blood CD4+ T cells defined an early proliferative response marker; a surge in PD-1+Ki-67+CD4+ T cells (≥1.5-fold from baseline after cycle 1) trended with worse PFS — inverting expectations from lung cancer and melanoma where such surges correlate with benefit PMID:38780927.
  • MKI67 (Ki-67) expression was measured in breast cancer samples undergoing whole-exome and RNA-seq profiling in a study that identified SF3B1 somatic mutations and splicing dysregulation PMID:22158541
  • Used as a cell-cycle (Ki67) marker by dual IHC in a mouse VHL-knockout model; VKO cells show increased Ki67 positivity vs ConKO (p=0.049), an effect absent when both HIFa isoforms are co-deleted PMID:23797736

Cancer types (linked)

  • ODG — Ki-67+ cells are rare (1.5–8%) and concentrated in the stem/progenitor compartment; used as IHC validation of the proliferative hierarchy PMID:27806376.
  • NBL — MKI67 expressed in proliferating hC1 postnatal adrenal progenitors, linking progenitor activity to the cholinergic cell-of-origin hypothesis for high-risk neuroblastoma PMID:34493726.
  • HNSC — PD-1+Ki-67+CD4+ T-cell surge used as peripheral blood pharmacodynamic biomarker in IMRT reirradiation + nivolumab trial; paradoxically associated with worse PFS PMID:38780927.

Co-occurrence and mutual exclusivity

  • In oligodendroglioma, MKI67+ cells co-express the stem/progenitor program (SOX2, SOX4, SOX11, NFIB, CCND2); differentiated oligo-like and astrocyte-like cells are MKI67-low PMID:27806376.
  • In HNSCC, MKI67 co-expressed with PDCD1 (PD-1) on CD4+ T cells as a peripheral immune pharmacodynamic marker PMID:38780927.

Therapeutic relevance

  • Ki-67 index in the stem/progenitor compartment of oligodendroglioma suggests this subpopulation drives tumor growth and may be the relevant therapeutic target PMID:27806376.
  • PD-1+Ki-67+CD4+ T-cell surge as a potential peripheral blood marker of immunotherapy response in HNSCC, though its utility as a predictive biomarker requires prospective validation given the paradoxical association with worse PFS PMID:38780927.

Open questions

  • Mechanism underlying the paradoxical association of Ki-67+PD-1+CD4+ T-cell surge with worse PFS in HNSCC reirradiation + nivolumab (regulatory T-cell skew? exhaustion? lymphatic drainage effects from prior irradiation?) is unresolved PMID:38780927.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:22158541

This page was processed by crosslinker on 2026-05-09. - PMID:23797736

This page was processed by crosslinker on 2026-05-09.