Intraoperative quantification of meningioma cell proliferation potential using rapid flow cytometry reveals intratumoral heterogeneity

Abstract

Background: Standard sampling methods to evaluate the proliferative ability of meningioma have not been established.

Methods: This prospective study was conducted to evaluate the effectiveness of intraoperative rapid flow cytometry (iFC) using raw samples for the quantitative assessment of proliferative ability in meningioma cells and to investigate intratumoral heterogeneity. Proliferation index (PI) was defined as the ratio of aneuploid cells with an abnormal number of chromosomes to the total cells.

Results: From 50 patients, 118 specimens were analyzed. There was a statistically significant correlation between the postoperative MIB-1 labeling index (LI) and PI (R = 0.59, P < 0.0001). A higher PI was correlated with a higher annual growth rate (AGR, cm³ /y) (R = 0.50, P = 0.0002, 26 patients). AGR showed a correlation with the intratumoral distribution of PI. PI was the highest at the center or the peripheral section of the tumor in tumors with high AGR, whereas it was highest at the dural attachment in tumors with low AGR (P = 0.039, n = 20). Pial feeders were more frequently observed when PI was high in the center or in the peripheral section (P = 0.006, n = 37).

Conclusions: Rapid iFC may thus become a substitute for MIB-1 LI. Intratumoral heterogeneity of cellular proliferative potential exists in meningiomas and is related to tumor biological characteristics such as AGR and development of pial feeders. This observation underscores the importance of standardization in the sampling method to accurately estimate the risk of meningioma recurrence.

Keywords: MIB-1; flow cytometry; meningioma; proliferative ability; recurrence.