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

Soichi Oya,Shunya Hanakita,Mizuho Inoue,Shinsuke Yoshida

doi:10.3390/curroncol29030134

Soichi Oya, Shunya Hanakita + Show 2 more

Open Access

https://doi.org/10.3390/curroncol29030134

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Abstract

This study sought to explore the existence and clinical significance of intratumoral heterogeneity of proliferative potential in vestibular schwannoma (VS). Rapid intraoperative flow cytometry was utilized with raw samples to measure the proliferative ability of VS. The proliferation index (PI) was defined as the ratio of the number of cells with greater than normal DNA content to the total number of cells. A total of 66 specimens (26 from the intrameatal portion and 40 from the cisternal portion) were obtained from 34 patients with VS. There was a moderate correlation between the PI and MIB-1 labelling index values (R = 0.57, p < 0.0001). In contrast, the patterns of heterogeneity, represented by the proportion of intrameatal PI to cisternal PI, were associated with tumor size (p = 0.03). In addition, preoperative hearing tended to be poor in cases where the intrameatal PI was higher than the cisternal PI (p = 0.06). Our data demonstrated the presence of intratumoral heterogeneity of proliferative potential in VS and its relationship with tumor characteristics. The results of this study may advocate the resection of the intrameatal portion of large VSs treated with planned subtotal resection, especially in cases of poor preoperative hearing function.

Highlights

In the treatment of brain tumors, it is vital to achieve the best balance between longterm tumor control and functional preservation
We aimed to explore whether intratumoral heterogeneity of proliferative potential exists in vestibular schwannoma (VS) and, if so, whether it is correlated with the risk of recurrence and clinical features
Because the aforementioned preliminary experiment demonstrated that Intraoperative flow cytometry (iFC) had a high quantitative ability, we investigated whether there was intratumoral heterogeneity of proliferation index (PI) by comparing the intrameatal and cisternal portions

Summary

Introduction

In the treatment of brain tumors, it is vital to achieve the best balance between longterm tumor control and functional preservation. For histologically benign tumors such as meningiomas and schwannomas, surgical risks should be carefully weighed against the benefits of excellent long-term tumor control and positive functional outcomes. For small- to medium-sized previously untreated VS, GKRS provided a tumor control rate of 92–98% during a follow-up of 10 years with a facial nerve complication rate of 1% or lower [2–4]. Treatment decisions for VS have been trending toward functional preservation rather than resection [5,6]. Small- to medium-sized VSs are often treated conservatively or with radiosurgery, whereas large VSs are frequently treated with subtotal resection (STR) followed by adjunctive radiosurgery for the best functional preservation of the facial nerve [7]. A subset of patients treated with STR eventually experience tumor recurrence that requires additional treatment [8,9]. Breshears, J.D. et al recently reported that residual tumors in the internal auditory meatus increased the risk of shorter progression-free survival [10]

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