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.

Quantitative Evaluation of Proliferative Potential Using Flow Cytometry Reveals Intratumoral Heterogeneity and Its Relevance to Tumor Characteristics in Vestibular Schwannomas

“…Another small study of 16 VS cases reported that an MIB-1 LI of 2% or higher was associated with a significantly shorter tumor doubling time [28]. Although one of the advantages of iFC is the high quantitative capability, as shown in our preliminary experiment and previous literature [11][12][13][14][15], our data failed to demonstrate the effectiveness of iFC in assessing the risk of recurrence. This might be because no tumor recurred after gross or near-total resection in our study, suggesting that the extent of resection has greater prognostic significance than the specific proliferative potential in the treatment of VSs.…”

“…In addition, the recurrence risk of histologically benign tumors should ideally be evaluated prospectively with a larger cohort and a follow-up period of 5-10 years. Third, although previous studies have shown that the PI is correlated with MIB-1 and WHO grading of meningiomas [11,13], the evaluation of the MIB-1 LI is subject to inter-and intra-observer biases inherent to the counting method. Finally, although we unified the location to obtain the cisternal specimen as the center of the portion in this study, there might also be heterogeneity inside the large cisternal portion.…”

“…In addition to standard histological diagnosis, we used iFC to assess the proliferative potential of tumor cells. We followed the previously reported detailed procedure for iFC [11]. Briefly, an approximately 2 mm specimen obtained during surgery was immediately (within an hour) sent to the laboratory, where it was immersed in a microtube with a kit solution (DNA Peak; Nihon Koden Corporation, Tokyo, Japan).…”

“…Their data raise the question of whether regional differences of proliferative potential exist in VS. Intraoperative flow cytometry (iFC) has been utilized to quantitatively assess the proliferative ability of brain tumor cells [11][12][13][14][15]. In the present study, we aimed to explore whether intratumoral heterogeneity of proliferative potential exists in VS and, if so, whether it is correlated with the risk of recurrence and clinical features.…”

Increased MIB-1 Labeling Index Is Associated with Abducens Nerve Morbidity in Primary Sporadic Petroclival Meningioma Surgery: Beyond Location and Approach

“…This novel approach enables a faster determination of the MIB-1 index and the proliferative potential intraoperatively [ 44 , 45 ]. Another interesting option to intraoperatively estimate the proliferative potential might be rapid flow cytometry which was found to be significantly correlated with the postoperative MIB-1 index in meningiomas [ 46 ]. Those methods might inform the surgical decision-making process regarding the weighting up the pros and cons of aggressive resection in terms functional preservation and provide a tailored therapy.…”