Non-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations.,Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC).,Unfortunately, most European cancer registries do not record individual types of NMSC.,To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers.,Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019.,We recorded 13,913 NMSCs occurring in 10,083 patients.,BCC represented 85.2% of all cases.,SCC patients were older than BCC patients (77.1 ± 11.3 years vs.,70.1 ± 12.3 years, p < 0.01).,The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes.,The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01).,The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01).,BCC and SCC are common malignancies developing at various ages and anatomical sites.,These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.
Calcineurin inhibitors such as cyclosporin A (CsA) are the mainstay of immunosuppressive treatment for organ transplant recipients.,Squamous cell carcinoma (SCC) of the skin is a major complication of treatment with these drugs, with a 65-100 fold higher risk than in the normal population1.,By contrast, the incidence of basal cell carcinoma (BCC), the other major keratinocyte-derived tumour of the skin, of melanoma and of internal malignancies increases to a significantly lesser extent 1.,Here we report that genetic and pharmacological suppression of calcineurin/NFAT function promotes tumour formation in mouse skin and in xenografts, in immune compromised mice, of H-rasV12 expressing primary human keratinocytes or keratinocyte-derived SCC cells.,Calcineurin/NFAT inhibition counteracts p53-dependent cancer cell senescence thereby increasing tumourigenic potential.,ATF3, a member of the “enlarged” AP-1 family, is selectively induced by calcineurin/NFAT inhibition, both under experimental conditions and in clinically occurring tumours, and increased ATF3 expression accounts for suppression of p53-dependent senescence and enhanced tumourigenic potential.,Thus, intact calcineurin/NFAT signalling is critically required for p53 and senescence-associated mechanisms that protect against skin squamous cancer development.