Ki-67 in meningioma: distribution and implications

Area of Science:

• Neuro-oncology
• Immunology
• Genomics

Background:

• Ki-67 is a key proliferation marker in meningiomas, crucial for prognosis and treatment decisions.
• Immune cell infiltration in meningiomas can complicate Ki-67 interpretation due to shared proliferative potential.
• Understanding the cellular source of Ki-67 is vital for accurate meningioma grading.

Purpose of the Study:

• To investigate the cellular origin and distribution of Ki-67 within the meningioma microenvironment.
• To explore the clinical, genomic, and biological associations of Ki-67 expression patterns.
• To refine the interpretation of Ki-67 as a prognostic marker in meningiomas.

Main Methods:

• Single-cell mass cytometry (CyTOF) and single-cell RNA sequencing (scRNAseq) profiled 32 meningiomas.
• Immunohistochemistry assessed Ki-67 index and mitotic count.
• Molecular Integrated Grade was established using CDKN2A/B deletion and chromosomal alterations; validation in 448 cases.

Main Results:

• Ki-67 expression was identified in both tumor and immune cells across 77,498 (CyTOF) and 45,460 (scRNAseq) cells.
• Cellular sources of Ki-67 shifted from myeloid cells in WHO grade 1 to non-immune tumor cells in grades 2 and 3.
• Elevated Ki-67 was noted in older patients (>70 years) and influenced by radiation; infarction and extramedullary hematopoiesis were identified as non-aggressive confounders.

Conclusions:

• Ki-67 expression in meningiomas is complex, originating from diverse cell types.
• Nuanced interpretation of Ki-67 indices is essential, considering potential confounding factors.
• Ki-67 remains a valuable prognostic marker when evaluated carefully within the tumor microenvironment.