Actinic keratosis and squamous cell carcinoma in the elderly. The increase in life expectancy and the change in the habits of the population with respect to UV exposure have led to an increase in the incidence of actinic keratosis (AK) and squamous cell carcinoma (SCC). There is no specific recommendation for the "frail" elderly, but they would not differ much from the recommendations of the younger subjects. AK are common: 1 in 3 men and 1 in 5 women after 70 years. In the absence of treatment, the AK can evolve towards a SCC, justifying the interest of a systematic and early management of the AK by cryotherapy (liquid nitrogen), dynamic phototherapy, cream containing 5-fluorouracil (5(FU), imiquimod or ingenuous mebutate. Incidence of SCC is also important in the elderly and especially in mans. It can be localized on skin or mucosa. There are forms of SCC in situ or Bowen disease, cutaneous or mucosal, accessible to cryotherapy, 5-FU, imiquimod or dynamic phototherapy as an alternative to surgery. The SCC presents a mainly local evolutionary risk, with involvement of adjacent noble organs, but also regional, with significant risk of lymph node metastases, and visceral (lungs, liver in particular). The treatment must be supervised by a multidisciplinary team. If the patient has cognitive disorders, the presence of the "person of trust" is possible. At best the presence of a geriatrician or onco-geriatrician is recommended. Most often active treatment will be considered and surgical excision is the standard treatment. If general anesthesia is required, the limitation may be at this time of management because of significant co-morbidities. For inoperable SCC radiotherapy and radiochemotherapy are sometimes proposed. Metastatic SCC is complex in elderly patients because chemotherapy is poorly tolerated.

Although most cutaneous squamous cell carcinomas (cSCCs) develop from actinic keratoses (AK), the key events in this evolution remain unclear. We have combined the results of different genomic and expression array platforms on matched concomitant samples of sun-exposed skin (SES), AK and cSCC from ten immunocompetent patients. Gene expression analysis and copy number alterations were assessed using GeneChip Human Gene 2.0 ST Array® (Affymetrix) and CytoScan HD Cytogenetics Solution® (Affymetrix) platforms, respectively. Integration of transcriptome and genome results was evaluated using the DR-Integrator tool. Additional studies (qPCR, immunohistochemistry and Western blot) were performed for selected genes. FOSL1 and BNC1 encode transcription factors whose expression was increased in cSCC in the expression array and the qPCR. By immunohistochemistry, FOSL1 showed an intense staining at the invasive front of cSCC samples and BNC1 expression varied from a nuclear (SES) to a cytoplasmic location (cSCC). Western blot analyses confirmed the enhancement of FOSL1 and BNC1. Additionally, the smallest overlapping regions of genomic imbalance (SORIs) involving at least 3 of the samples were selected. One of the SORIs was a deletion in the p24.1 band of chromosome 3, shared by 7 of the cSCCs. A strong correlation in the integration analysis was found for NEK10, a gene contained in the previously mentioned SORI. Loss of NEK10 expression in cSCC was confirmed by immunohistochemistry and Western blot analyses. In addition, functional studies in NEK10 depleted cells were performed. In conclusion, we identified FOSL1 and BNC1, which could act as tumor drivers, and NEK10, which could function as a tumor suppressor, to be differentially expressed during cSCC development. This article is protected by copyright. All rights reserved.