1. p53 protein expression patterns associated with TP53 mutations in breast carcinoma.
- Author
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Anderson SA, Bartow BB, Harada S, Siegal GP, Wei S, Dal Zotto VL, and Huang X
- Subjects
- Humans, Female, Middle Aged, Adult, Aged, Immunohistochemistry, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, High-Throughput Nucleotide Sequencing, Aged, 80 and over, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Breast Neoplasms genetics, Breast Neoplasms pathology, Breast Neoplasms metabolism, Mutation
- Abstract
Purpose: The importance of a TP53 mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with TP53 mutations in breast cancers from 64 patients., Methods: TP53 mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC)., Results: Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A TP53 mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a TP53 mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (p < 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense TP53 mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (p < 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (p < 0.05)., Conclusion: These findings suggest that p53 IHC can be a potential surrogate for TP53 mutations in BC. Different p53 expression patterns may correlate with specific TP53 genetic mutations in BC., (© 2024. The Author(s).)
- Published
- 2024
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