Dataset Information

The predictive capability of immunohistochemistry and DNA sequencing for determining TP53 functional mutation status: a comparative study of 41 glioblastoma patients.

ABSTRACT: 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.

SUBMITTER: Roshandel AK

PROVIDER: S-EPMC6817445 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The predictive capability of immunohistochemistry and DNA sequencing for determining <i>TP53</i> functional mutation status: a comparative study of 41 glioblastoma patients.

Roshandel Aarash K AK Busch Christopher M CM Mullekom Jennifer Van JV Cuoco Joshua A JA Rogers Cara M CM Apfel Lisa S LS Marvin Eric A EA Sontheimer Harald W HW Umans Robyn A RA

Oncotarget 20191022 58

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 <i>TP53</i> gene product. Here, we examined the relationship between p53 immunorea ...[more]

PMID: 31692772

Similar Datasets

Project description:TP53 mutations are ubiquitous in high-grade serous ovarian carcinomas (HGSOC), and the presence of TP53 mutation discriminates between high and low-grade serous carcinomas and is now an important biomarker for clinical trials targeting mutant p53. p53 immunohistochemistry (IHC) is widely used as a surrogate for TP53 mutation but its accuracy has not been established. The objective of this study was to test whether improved methods for p53 IHC could reliably predict TP53 mutations independently identified by next generation sequencing (NGS). Four clinical p53 IHC assays and tagged-amplicon NGS for TP53 were performed on 171 HGSOC and 80 endometrioid carcinomas (EC). p53 expression was scored as overexpression (OE), complete absence (CA), cytoplasmic (CY) or wild type (WT). p53 IHC was evaluated as a binary classifier where any abnormal staining predicted deleterious TP53 mutation and as a ternary classifier where OE, CA or WT staining predicted gain-of-function (GOF or nonsynonymous), loss-of-function (LOF including stopgain, indel, splicing) or no detectable TP53 mutations (NDM), respectively. Deleterious TP53 mutations were detected in 169/171 (99%) HGSOC and 7/80 (8.8%) EC. The overall accuracy for the best performing IHC assay for binary and ternary prediction was 0.94 and 0.91 respectively, which improved to 0.97 (sensitivity 0.96, specificity 1.00) and 0.95 after secondary analysis of discordant cases. The sensitivity for predicting LOF mutations was lower at 0.76 because p53 IHC detected mutant p53 protein in 13 HGSOC with LOF mutations. CY staining associated with LOF was seen in 4 (2.3%) of HGSOC. Optimized p53 IHC can approach 100% specificity for the presence of TP53 mutation and its high negative predictive value is clinically useful as it can exclude the possibility of a low-grade serous tumour. 4.1% of HGSOC cases have detectable WT staining while harboring a TP53 LOF mutation, which limits sensitivity for binary prediction of mutation to 96%.

Dataset Information

The predictive capability of immunohistochemistry and DNA sequencing for determining TP53 functional mutation status: a comparative study of 41 glioblastoma patients.

Publications

The predictive capability of immunohistochemistry and DNA sequencing for determining <i>TP53</i> functional mutation status: a comparative study of 41 glioblastoma patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets