Prognostic significance of nuclear DNA content in human neuroepithelial tumors

Abstract

The relationship between survival and flow cytometric DNA-ploidy and other prognostic factors such as histological subtype, anatomical tumor site, patient sex and age was investigated in 153 patients with intracranial neuroepithelial tumors who underwent surgical treatment. We found a trend toward poorer survival from anaplastic astrocytomas and glioblastomas with respect to low-grade (I and II) astrocytomas (which did not differ significantly); accordingly, patients were grouped into these 3 histologic subgroups. Thirty-seven of the 153 tumors (24.2%) were aneuploid with a median DNA-index (DI) of 1.3 (range: 1.2-2.0). DNA-ploidy correlated with histology, since anaplastic astrocytomas and glioblastomas were significantly (p = 0.041) more frequently aneuploid (around 30%) than low-grade astrocytomas (around 10%). Patients with DNA-aneuploid tumors (i.e., with DI not equal to 1.00) survived for a shorter time (31.4 weeks) than patients with DNA diploid tumors (75.1 weeks) (p less than 0.001). This difference was confirmed by Cox's multivariate analysis. Aneuploid tumors were associated with a poorer survival (p = .0002) when compared with diploid tumors, resulting in a relative risk point estimate (RR) of 2.41, 95% confidence interval (Cl) = 1.55-3.74. Histological subtype was also significantly associated with survival (p less than 0.0001), with RRs of 2.09, 95% Cl = 1.13-3.86 and 3.59, 95% Cl = 1.96-6.59 for anaplastic astrocytomas and glioblastomas, respectively, compared to low-grade astrocytomas. We therefore suggest that the flow cytometric measurement of DNA-ploidy has relevant significance in predicting survival in patients treated for intracranial neuroepithelial tumors.

Clinicopathologic study of 85 similarly treated patients with anaplastic astrocytic tumors

“…Like with several other variables, conclusions about ploidy as a prognostic variable in astrocytic tumors are mixed and are sometimes contradictory. Whereas a number of investigators found that aneuploidy was associated with shorter survival,33, 34, 46–48 others found no association,49 and still others observed longer survivals 15, 50. In our series, aneuploidy was associated with younger patient age and longer survival time.…”

On-line Flow Cytometry for Real-time Surgical Guidance

“…Aberrations in the DNA content (ploidy) or increase in DNA synthesis during the S and G 2 -M phases of the cell cycle can be evaluated rapidly by DNA-FC. Oncological studies have shown that 30 to 80% of all malignant gliomas have aneuploid cell populations (4,7,8,13), and for gliomas with normal ploidy, elevated percentages of cells in S and G 2 -M phases have been correlated with poor outcome (6,21,27). Consequently, malignant tissue can be identified by the presence of aneuploid populations of cells and/or by the presence of an elevated level of S phase and G 2 -M phase cells.…”

Prognostic Significance of Histologic and Cytometric Factors in Supratentorial Astrocytomas

“…While it is well defined that well differentiated tumors (A) are diploid [15,30], in dealing with high-grade gliomas, the results vary in the different series. Some authors could not find a prognostic relationship between ploidy and tumor progression [15], whereas in other reports diploid and tetraploid tumors are associated with a better prognosis [13,14]. Studies are discrepant, and some authors find that diploidy in GBM means a quicker progression [31].…”

“…radiotherapy, patient's age, or Karnofsky score [10][11][12]. There are also a few studies on the DNA pattern measured by flow cytometry [13][14][15] or by image analysis [16][17][18], but the results are inconclusive, whereas some authors find a high correlation between ploidy and prognosis, the relationship seems to be lost in multivariate analysis.…”