Analysis of homozygous deletion of the p16 gene and correlation with survival in patients with glioblastoma multiforme

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Object. One of the most frequent genetic abnormalities found in patients with glioblastoma multiforme (GBM) is homozygous deletion of the p16 tumor suppressor gene. The authors investigated whether this deletion is associated with prognosis in patients with GBM.

Methods. In 46 adult patients with supratentorial GBM, homozygous deletion of the p16 gene in tumor DNA was examined using the multiplex polymerase chain reaction assay. The deletion was confirmed in 14 (30.4%) of 46 patients, eight (30.8%) of 26 men and six (30.0%) of 20 women. Cox proportional hazard regression analysis, adjusted for age at surgery, the Karnofsky Performance Scale score, extent of resection, and the MIB-1 labeling index, revealed that homozygous deletion of the p16 gene was significantly associated with overall survival and progression-free survival in men, but not in women.

Conclusions. The results of this study suggest that p16 homozygous deletion is a significant unfavorable prognostic factor in male patients with GBM.

Article Information

Address reprint requests to: Takanori Kamiryo, M.D., Department of Neurosurgery, Kumamoto University Medical School, 1–1–1 Honjo, Kumamoto 860–8556, Japan. email: tkamiryo-nsu@umin.ac.jp.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    The results of multiplex PCR for titration using normal human DNA and glioma DNA with known homozygous deletion of the p16 gene (U251-MG) are shown. A marked reduction of the p16 amplimer (upper band) compared with the control 9qSTS amplimer (lower band) was noted when the normal DNA constituted less than 20% of total DNA.

  • View in gallery

    Graph showing a standard curve presenting the relative ratio of band intensity of p16/9qSTS against the percentage of normal DNA. Bars represent two standard deviations.

  • View in gallery

    Representative results of multiplex PCR when using p16 and 9qSTS primers. Samples shown in Lanes 1, 2, and 4 were obtained from patients with and Lanes 3 and 5 from patients without homozygous deletion of the p16 gene. The p16/9qSTS ratio is indicated under each lane. Upper band, p16; lower band, 9qSTS; M, size marker.

  • View in gallery

    Graphs showing the correlation of p16 homozygous deletion with survival time in patients with GBM. Kaplan—Meier curves depict survival time from initial surgery for 46 patients (A), 26 men (B) and 20 women (C). The median survival time of each group is shown in brackets. Probability values are shown.

  • View in gallery

    Graphs showing correlation of p16 homozygous deletion with progression-free survival time in patients with GBM. Kaplan—Meier curves show time to progression from the initial surgery for 43 patients (A), 24 men (B) and 19 women (C). The median survival time of each group is shown in brackets. Probability values are shown.

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