N.A. Oleynikova1, T.Yu. Zavidnyi2, P.G. Malkov3, O.A. Kharlova4, N.V. Danilova5

1-5 Lomonosov Moscow State University (Moscow, Russia)

The p63 gene is a member of the p53 tumor suppressor gene family. However, in contrast to the role of the main gene of the family in carcinogenesis, the role of the p63 gene in the initiation and progression of tumor growth remains unclear: in some cases, this gene seems to be a tumor-suppressor gene, and in others it seems to be an oncogene. There are many studies reporting the presence of a predictive value of p63 expression in some types of cancer, however, results of such studies are often contradictory. Here, we reviewed the characteristics of the p63 gene and its products, including several protein isoforms, which have different physiological roles and different significance in carcinogenesis. It also characterizes the current and promising applications in the diagnosis of neoplasms using immunohistochemistry. The data of various studies aimed at finding the relation between prognosis and p63 expression in tumor cells are considered with special attention. 

The p63 gene encodes for two main isoforms by alternative promoters (ΔNp63 and TAp63). The structure of TAp63 isoforms includes N-terminal transactivation domain, while ΔNp63s possess a shorter N-terminal region. Due to the presence of this domain, TAp63s have a functional similarity to the p53 protein. ΔNp63 is mostly needed during skin development and for tissue proliferation in multiple organs. In contrast, TAp63 is poorly expressed in somatic cells and is required mainly in embryogenesis. 

The various roles of p63 in carcinogenesis are unevenly distributed among its isoforms. The ΔNp63 isoforms are highly expressed in many types of cancer. They are primarily responsible for stimulating the initiation and progression of tumor growth. TAp63 predominantly acts as a tumor suppressor. It should be noted that opposite roles in carcinogenesis are shown for certain types of tumor lesions for both groups of isoforms. 

P63 immunohistochemistry has several common applications in pathologic diagnosis. First of all, p63 is used as a myoepithelial and basal cell marker. Positive p63 expression can rule out invasion in breast tumors and confirm diagnosis of prostatic adenocarcinoma. On the other hand, p63 can be a marker of squamous differentiation of lung cancer. The prognostic significance of p63 expression is discussed using the example of colon neoplasms, lung adenocarcinoma, bladder urothelial cancer and oral cavity lesions.

Oleynikova N.A., Zavidnyi T.Yu., Malkov P.G., Kharlova O.A., Danilova N.V. Prognostic value and role in carcinogenesis and tumor`s diagnostic of p63 gene and its protein products. Technologies of Living Systems. 2021. V. 18. № 2. Р. 27−37. DOI: https://doi.org/10.18127/j20700997-202103-02 (in Russian).

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