The predictive capability of immunohistochemistry and DNA sequencing for determining TP53 functional mutation status: a comparative study of 41 glioblastoma patients
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Aarash K. Roshandel1,2,*, Christopher M. Busch2,3,4,5,*, Jennifer Van Mullekom6, Joshua A. Cuoco4,5, Cara M. Rogers3,4,5, Lisa S. Apfel3,4,5, Eric A. Marvin3,4,5, Harald W. Sontheimer2,3 and Robyn A. Umans2
1 College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, VA 24061, USA
2 The Fralin Biomedical Research Institute at VTC, Roanoke, VA 24016, USA
3 Virginia Tech School of Neuroscience, Blacksburg, VA 24061, USA
4 Carilion Clinic, Division of Neurosurgery, Roanoke, VA 24014, USA
5 Edward Via College of Osteopathic Medicine, Blacksburg, VA 24060, USA
6 Department of Statistics (MC0439), Hutcheson Hall, Blacksburg, VA 24061, USA
* These authors contributed equally to this work
|Robyn A. Umans,||email:||[email protected]|
Keywords: p53; TP53; immunohistochemistry; gene sequencing; glioblastoma multiforme
Received: January 19, 2019 Accepted: September 10, 2019 Published: October 22, 2019
Tumor protein 53 (p53) regulates fundamental pathways of cellular growth and differentiation. Aberrant p53 expression in glioblastoma multiforme, a terminal brain cancer, has been associated with worse patient outcomes and decreased chemosensitivity. Therefore, correctly identifying p53 status in glioblastoma is of great clinical significance. p53 immunohistochemistry is used to detect pathological presence of the TP53 gene product. Here, we examined the relationship between p53 immunoreactivity and TP53 mutation status by DNA Sanger sequencing in adult glioblastoma. Of 41 histologically confirmed samples, 27 (66%) were immunopositive for a p53 mutation via immunohistochemistry. Utilizing gene sequencing, we identified only eight samples (20%) with TP53 functional mutations and one sample with a silent mutation. Therefore, a ≥10% p53 immunohistochemistry threshold for predicting TP53 functional mutation status in glioma is insufficient. Implementing this ≥10% threshold, we demonstrated a remarkably low positive-predictive value (30%). Furthermore, the sensitivity and specificity with ≥10% p53 immunohistochemistry to predict TP53 functional mutation status were 100% and 42%, respectively. Our data suggests that unless reliable sequencing methodology is available for confirming TP53 status, raising the immunoreactivity threshold would increase positive and negative predictive values as well as the specificity without changing the sensitivity of the immunohistochemistry assay.
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