p63 expression in normal skin and usual cutaneous carcinomas

Abstract

Background: p63 is a p53 homologue that is mapped to chromosome 3q27. This gene encodes six different isoforms, which have either transactivating or dominant negative effects on p53‐reporter genes. It has been described that in contrast to p53, p63 seems not to be associated with tumor predisposition, as neither p63 knockout mouse models nor germline p63 mutations are related to an increased risk of tumorigenesis. It has been demonstrated that p63 is a reliable keratinocyte stem cell marker and that it is involved in the maintenance of the stem cell population. Scant data on p63 expression in normal skin, basal cell carcinomas (BCCs), keratoacanthomas and squamous cell carcinomas (SCCs) have been reported. We herein evaluated p63 expression in 16 BCCs, one keratoacanthoma and 13 SCCs. Methods: Immunohistochemistry according to the streptavidin‐biotin‐peroxidase technique, using the antibody 4A4 raised against all p63 isoforms, was performed. p63 expression was evaluated in epidermal cells and skin appendages. Semi‐quantitative evaluation (–, +, ++, +++) of p63 expression in BCCs, keratoacanthoma and SCCs was carried out. Only nuclear expression was considered as specific. Results: p63 was expressed in the nuclei of epidermal basal and suprabasal cells, in the cells of the germinative hair matrix and the external root sheath of hair follicles, in the basal cells of the sebaceous gland and in the myoepithelial/basal cells of the sweat glands. All terminally differentiated cells were negative for p63. All BCCs showed ++ to +++ immunoreactivity. At variance, keratoacanthomas and grade I and II SCCs showed variable p63 reactivity in a basal layer‐like distribution, whereas undifferentiated cells of grade III SCCs showed ++ to +++ positivity. A grade IV spindle SCC showed + immunoreactivity. The SCCs in situ showed remarkable expression of p63 in all cell layers. Terminally differentiated squamous cells were either negative or showed only focal immunoreactivity in the carcinomas. Conclusions: p63 is consistently expressed in the basal cells of epidermis and cutaneous appendages, including the basal/myoepithelial cells of sweat glands. Based on our findings, the balance of probabilities favors that p63 might play a role in the pattern of differentiation and in the oncogenesis of usual carcinomas of the skin.

Impaired repair of cyclobutane pyrimidine dimers in human keratinocytes deficient in p53 and p63

“…p63 clearly plays a critical role in epidermal development and homeostasis both in mice and humans (15)(16)(17), but it is still unclear if p63 plays a role in carcinogenesis. While p63 has been reported to be absent or reduced in some human cancers, including basal cell carcinomas (18), it has more frequently been reported to be overexpressed in various tumors (19,20), including non-melanoma skin cancers (21)(22)(23)(24). Similarly, conflicting data from mice heterozygous for p63 have not resolved whether p63 is a tumor suppressor or oncogene (25)(26)(27).…”

Expression of p63 in primary cutaneous adnexal neoplasms and adenocarcinoma metastatic to the skin

“…Kaufmann et al The expression of p63 in normal human epidermis, cutaneous appendages and skin carcinomas has been recently assessed. [16][17][18] p63 seems to play a major role in ectodermal development, in the maintenance of the basal cell population of stratified epithelia, and also in the terminal differentiation of epithelia. [6][7][8] In vitro studies, using transformed human keratinocytes, have shown that p63 is a nuclear transcription factor that triggers keratinocyte differentiation and is downregulated in terminally differentiated cells.…”

“…10,12,14 The expression of p63 in normal human epidermis, cutaneous appendages and skin carcinomas has been recently assessed. 16,17 In these studies, p63 was detected in the epidermal and adnexal basal/ myoepithelial cells and it has been suggested that p63 might be used as a diagnostic marker for epidermal or adnexal tumors in the skin. [16][17][18] Cutaneous metastases may be the initial manifestation of some neoplasms, including adenocarcinomas.…”

“…16,17 In these studies, p63 was detected in the epidermal and adnexal basal/ myoepithelial cells and it has been suggested that p63 might be used as a diagnostic marker for epidermal or adnexal tumors in the skin. [16][17][18] Cutaneous metastases may be the initial manifestation of some neoplasms, including adenocarcinomas. The distinction between such metastases and primary cutaneous neoplasms, especially adnexal tumors, on histologic grounds alone, may be difficult.…”

Telomerase expression and proliferative activity suggest a stem cell role for thyroid solid cell nests

“…[2][3][4] It has been advanced that p63 plays a role in triggering the differentiation of some specific cell lineages. [2][3][4][5][6][7] We have previously shown that p63 and basal keratins are restricted to the main cells, being negative in the C cells and in other thyroid structures, and advanced that the main cells of the solid cell nests display a basal/stem cell phenotype. 8 Bcl-2 overexpression has also been associated with stem cells.…”