Department of Pathology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan.
Pathobiology. 2024;91(3):230-243. doi: 10.1159/000535203. Epub 2023 Nov 14.
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.
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.
Immunohistochemistry of oncogenic signals should be interpreted according to molecular findings based on genomic oncology, in addition to the microscopic findings of diagnostic pathology.
观察在科学发展中起着关键作用，包括病理学。通过将疾病（如癌症）分解为更小的器官、组织、细胞和分子来分析其病因。目前癌症诊断的标准程序——显微镜观察，依赖于保存的形态特征。相比之下，分子分析则探索导致基因突变为和异常蛋白表达的致癌途径激活。这些分子分析有可能确定治疗靶点，并在临床肿瘤学中受到广泛关注。
本文总结了 p53 通路的主要生物标志物，包括 p53、p16 和鼠双微体 2（MDM2），并结合传统外科病理学和新兴的基因组肿瘤学进行了讨论。p53 通路在超过一半的癌症中失调，可应用于多种诊断情况。还描述了一种基于基因状态的免疫表型的四分类模型、每种 p53 通路基因异常发生频率较高的肿瘤类型以及最小化的 p53 通路免疫组化面板。
除了诊断病理学的显微镜发现外，基于基因组肿瘤学的分子发现，应根据致癌信号的免疫组织化学来进行解释。
