Evaluation of DNA ploidy with intraoperative flow cytometry may predict long-term survival of patients with supratentorial low-grade gliomas: Analysis of 102 cases

Clin Neurol Neurosurg. 2018 May:168:46-53. doi: 10.1016/j.clineuro.2018.02.027. Epub 2018 Feb 21.

Abstract

Objective: The objective of the present study was evaluation of the prognostic significance of DNA ploidy assessed with intraoperative flow cytometry (iFC) during resection of low-grade gliomas (LGG).

Patients and methods: Retrospective analysis of 102 consecutive cases of newly diagnosed WHO grade II supratentorial gliomas, surgical removal of which was accompanied by iFC, was done. There were 46 diffuse astrocytomas (DA) and 56 oligodendrogliomas (OD). According to iFC, 68 tumors (67%) were considered non-aneuploid and 34 (33%) aneuploid. Median extent of resection (EOR) was 95% (mean, 89.0 ± 14.5%). Postoperative FRT with or without adjuvant chemotherapy was administered in 24 cases (24%).

Results: With median follow-up of 29.9 months (range, 9.4-66.9 months), neither median overall survival (OS) nor median progression-free survival (PFS) were reached. The 3-year actuarial OS and PFS rates were 95.8% and 86.3%, respectively. Non-aneuploid DNA histogram type of the tumor was associated with significantly longer OS both in univariate (P = 0.0094) and multivariate (P = 0.0232) analyses, and with longer PFS in univariate analysis (P = 0.0184). Aneuploidy was encountered more frequently in DA, than in OD (43% vs. 25% of cases; P = 0.0488). Tumor progression was noted in 15 DA and 4 patients succumbed to the disease; in this subgroup the main unfavorable prognostic factors for OS and PFS were presence of aneuploidy (P = 0.0510) and MIB-1 index ≧3.9% (P = 0.0141), respectively. Aneuploid DA more frequently progressed to glioblastoma than to anaplastic astrocytoma, but this difference did not reach statistical significance (P = 0.1362). In contrast, only one OD progressed (non-aneuploid neoplasm), and no one patient with such tumor died of the disease.

Conclusions: DNA ploidy assessed with iFC may be effectively used as prognostic indicator in cases of LGG, especially of DA. Aneuploid tumors demonstrate more aggressive clinical course translated into shorter OS of patients. Thus, their detection during surgery may be helpful for decision on the optimal EOR, and for choice of the most appropriate postoperative adjuvant therapy.

Keywords: DNA aneuploidy; DNA content; DNA ploidy; Flow cytometry; Low-grade glioma; Malignant transformation; Prognostic factors; Survival.

MeSH terms

  • Adult
  • Aged
  • Astrocytoma / mortality
  • Astrocytoma / surgery*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / surgery
  • DNA*
  • Disease-Free Survival
  • Female
  • Flow Cytometry* / methods
  • Glioma / surgery
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neurosurgical Procedures / methods*
  • Oligodendroglioma / pathology

Substances

  • DNA