Immunohistochemical correlates of TP53 somatic mutations in cancer

Abstract

Despite controversy on the correlation between p53 accumulation and TP53 mutational status, immunohistochemical (IHC) detection of overexpressed protein has long been used as a surrogate method for mutation analysis. The aim of our study was to characterise the IHC expression features of TP53 somatic mutations and define their occurrence in human cancers. A large-scale database analysis was conducted in the IARC TP53 Database (R17); 7878 mutations with IHC features were retrieved representing 60 distinct tumour sites. The majority of the alterations were immunopositive (p <0.001). Sex was known for 4897 mutations showing a female dominance (57.2%) and females carrying negative mutations were significantly younger. TP53 mutations were divided into three IHC groups according to mutation frequency and IHC positivity. Each group had female dominance. Among the IHC groups, significant correlations were observed with age at diagnosis in breast, bladder, liver, haematopoietic system and head & neck cancers. An increased likelihood of false negative IHC associated with rare nonsense mutations was observed in certain tumour sites. Our study demonstrates that p53 immunopositivity largely correlates with TP53 mutational status but expression is absent in certain mutation types.Besides, describing the complex IHC expression of TP53 somatic mutations, our results reveal some caveats for the diagnostic practice.