The predictive capability of immunohistochemistry and DNA sequencing for determining functional mutation status: a comparative study of 41 glioblastoma patients.

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 gene product. Here, we examined the relationship between p53 immunoreactivity and 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 functional mutations and one sample with a silent mutation. Therefore, a ≥10% p53 immunohistochemistry threshold for predicting 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 functional mutation status were 100% and 42%, respectively. Our data suggests that unless reliable sequencing methodology is available for confirming 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.