Quantitative Evaluation of Proliferative Potential Using Flow Cytometry Reveals Intratumoral Heterogeneity and Its Relevance to Tumor Characteristics in Vestibular Schwannomas - PubMed (original) (raw)

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

Soichi Oya et al. Curr Oncol. 2022.

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.

Keywords: MIB-1; flow cytometry; heterogeneity; proliferative potential; vestibular schwannoma.

PubMed Disclaimer

Conflict of interest statement

This study was conducted under a collaborative research agreement between Saitama Medical University and Nihon Kohden Corporation for the voluntary lease of the pipetting device for tissue preparation. All authors declare that they have no conflict of interest.

Figures

Figure 1

Figure 1

DNA ploidy analysis using intraoperative flow cytometry. The horizontal axis represents the intensity of propidium iodide fluorescence. Peak A indicates the cluster of G0G1-phase (diploid) cells, whereas Peak B represents that of tetraploid G2/M-phase cells. The proliferation index was defined as the ratio of the number of cells with greater-than-normal DNA content (P2) to the total number of cells (P1).

Figure 2

Figure 2

(A) Correlation between the proliferation index (PI) and MIB-1 labelling index (R = 0.57, p < 0.0001). (B) PI are plotted on the left (intrameatal portion) and right (cisternal portion) columns. Specimens from the same tumor are denoted by straight lines. (C) Delta PI (intrameatal portion–cisternal portion) are plotted. Note that most tumors demonstrate intratumoral heterogeneity in the PI.

Figure 3

Figure 3

Illustrative case 1. (A) A representative case of vestibular schwannoma causing severe hearing loss. The proliferation index (PI) appears to be significantly higher in the (B) intrameatal portion than in the (C) cisternal portion: 29.2% vs. 11.7%. Arrows represent the peaks of tetraploid cells.

Figure 4

Figure 4

Illustrative case 2. (A) A representative case of solid vestibular schwannoma with serviceable hearing. The proliferation index (PI) appears to be significantly lower in the (B) intrameatal portion than in the (C) cisternal portion: 4.7% vs. 17.2%. Arrows represent the peaks of tetraploid cells.

References

    1. Seferis C., Torrens M., Paraskevopoulou C., Psichidis G. Malignant Transformation in Vestibular Schwannoma: Report of a Single Case, Literature Search, and Debate. J. Neurosurg. 2014;121:160–166. doi: 10.3171/2014.7.GKS141311. -DOI -PubMed
    1. Hasegawa T., Kida Y., Kato T., Iizuka H., Kuramitsu S., Yamamoto T. Long-Term Safety and Efficacy of Stereotactic Radiosurgery for Vestibular Schwannomas: Evaluation of 440 Patients More Than 10 Years after Treatment with Gamma Knife Surgery. J. Neurosurg. 2013;118:557–565. doi: 10.3171/2012.10.JNS12523. -DOI -PubMed
    1. Kondziolka D., Mousavi S.H., Kano H., Flickinger J.C., Lunsford L.D. The Newly Diagnosed Vestibular Schwannoma: Radiosurgery, Resection, or Observation? Neurosurg. Focus. 2012;33:E8. doi: 10.3171/2012.6.FOCUS12192. -DOI -PubMed
    1. Lunsford L.D., Niranjan A., Flickinger J.C., Maitz A., Kondziolka D. Radiosurgery of Vestibular Schwannomas: Summary of Experience in 829 Cases. J. Neurosurg. 2005;102:195–199. doi: 10.3171/sup.2005.102.s_supplement.0195. -DOI -PubMed
    1. Schwartz M.S., Kari E., Strickland B.M., Berliner K., Brackmann D.E., House J.W., Friedman R.A. Evaluation of the Increased Use of Partial Resection of Large Vestibular Schwannomas: Facial Nerve Outcomes and Recurrence/Regrowth Rates. Otol. Neurotol. 2013;34:1456–1464. doi: 10.1097/MAO.0b013e3182976552. -DOI -PubMed

MeSH terms

LinkOut - more resources