Pan-cancer analysis of p53 immunohistochemical staining

Abstract

Cancer is a disease of genetic dysregulation. It is little wonder, then, that p53, which plays a central role in regulating the cell’s response to DNA damage, is one of the most frequently mutated genes across many cancer types. Normal, healthy cells constitutively express low levels of p53, detectable immunohistochemically as weak staining rather than complete negativity. However, previous work has shown that in breast cancer, extreme positive or negative staining for p53 were both correlated with worse overall survival and p53 mutation when compared to cases with weak p53 staining. This extreme expression phenotype may serve as a simple and cost-effective biomarker for p53 mutation and poor prognosis in breast cancer, but it remains unclear how applicable it may be to other cancer types. While p53 mutation is common across many cancer types, mutation rates vary greatly, implying potential differences in the underlying biology. In this study, we tried to replicate the extreme expression analysis of p53 staining across multiple cancer types to see whether this could be a part of a universal biomarker of cancer or if instead there are fundamental differences in p53 biology between different cancer types. Leveraging our framework for integrated, multimodal biomarker discovery and validation, Pathology Integromics in Cancer (PICan), we found that similar correlations between p53 extreme expression and survival might be found in other cancer types as well. Further work will be needed to verify whether the same underlying biochemistry is at play.