In gratitude of the loyal support of our members, the CNS is offering complimentary 2021 Annual Meeting registration to all members! Learn more.

  • Immunohistochemistry is Not a Sufficient Method of Determining p53 Mutation in Glioblastoma

    Final Number:
    2030

    Authors:
    Gary R. Simonds MD, MHCDS, FAANS; Chris Busch MD; Robyn Umans; Aarash Roshandel; Eric Marvin; Harald Sontheimer PhD; Michael John Benko; Cara Rogers MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2018 Annual Meeting

    Introduction: P53 is a tumor suppressor gene that helps regulate the cell cycle. The gene is involved in DNA repair and programmed cell death. Mutations of this gene are often associated with various cancers. The importance of p53 mutational status remains controversial in regards to prognosis for Glioblastoma (GBM). Nevertheless, some studies suggest that p53 mutation carries a worse prognosis. Laboratories frequently employ immunohistochemistry (antibody clone (DO-7)) to determine p53 positivity. Many use a 10% nuclear staining threshold to imply p53 mutation positivity. We question whether this form of assay is sensitive and specific enough in the determination of this potentially important mutation.

    Methods: Standard laboratory results on p53 immunohistochemical staining were obtained on 34 glioblastoma tissue samples. We utilized Sanger gene sequencing methodology to determine actual p53 mutations within the same samples. We compared reported laboratory-derived percent nuclear antibody staining with actual gene sequencing-determined mutations.

    Results: Out of our 34 histologically confirmed GBM samples, 21 were deemed “positive” for p53 mutation via laboratory immunohistochemistry. That is, they were found to have greater than 10% of their nuclei staining positive, implying that 62% of the tumors had p53 mutations. Utilizing gene sequencing, we identified only six with actual p53 mutations (18%). In the samples with actual p53 mutations, nuclear antibody staining was on the order of 75% (average).

    Conclusions: Our study suggests that a 10% threshold for nuclear staining in immunohistochemical assays for p53 mutation is too low, and will result in a high rate of false positivity. We would suggest a much higher threshold. More to the point, we believe that gene sequencing should be the principal method employed in determining p53 mutational status.

    Patient Care: More accurate determination of p53 may have a significant impact on determining prognosis in GBM patients.

    Learning Objectives: to understand that antibody staining for p53 mutation in glioblastoma may have high rates of false positive. to understand that gene sequencing is a preferred method for determining p53 mutational positivity p53 may correlate with bad prognosis in gbm

    References:

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy