The Pathology according to p53 Pathway

Abstract

<b><i>Background:</i></b> Observations play a pivotal role in the progress of science, including in pathology. The cause of a disease such as cancer is analyzed by breaking it down into smaller organs, tissues, cells, and molecules. The current standard cancer diagnostic procedure, microscopic observation, relies on preserved morphological characteristics. In contrast, molecular analyses explore oncogenic pathway activation that leads to genetic mutations and aberrant protein expression. Such molecular analyses could potentially identify therapeutic targets and has gained considerable attention in clinical oncology. <b><i>Summary:</i></b> This review summarizes the cardinal biomarkers of the p53 pathway, p53, p16, and mouse double minute 2 (MDM2), in the context of traditional surgical pathology and emerging genomic oncology. The p53 pathway, which is dysregulated in more than a half of all cancers, can be applied in several diagnostic settings. A four-classification model of immunophenotype for p53 pathway gene status, tumor types with a high frequency of abnormalities for each p53 pathway gene, and a minimal p53 pathway immunohistochemical panel is also described. <b><i>Key Messages:</i></b> Immunohistochemistry of oncogenic signals should be interpreted according to molecular findings based on genomic oncology, in addition to the microscopic findings of diagnostic pathology.