Ingenol mebutate-mediated reduction in p53-positive keratinocytes in skin cancerization field directly correlates with clinical response in patients with multiple actinic keratoses

Journal of the European Academy of Dermatology and Venereology : JEADV
V GrandiN Pimpinelli

Abstract

UV radiation represents the main risk factor for non-melanoma skin cancers. Chronic UV exposure induces 'p53 patches', i.e. clonal outgrowths of keratinocytes with high nuclear expression of mutated p53, which might progress to actinic keratosis (AK) and ultimately squamous cell carcinomas (SCCs). Analysis of ingenol mebutate gel (150 and 500 mcg/g) effects in the reduction in 'p53 patches' inside skin cancerization field (CF) in patients with multiple AKs of face/scalp or trunk/extremities, in order to investigate whether the expected reduction in p53+ keratinocytes might have a direct role in the long-term AK reduction in treated areas. We enrolled n = 10 patients, treated with ingenol mebutate and evaluated at 2 and 6 months after treatment. We observed clinical responses in the majority of patients (n = 7), with AK reduction or complete clearance (n = 6 and n = 1, respectively). Notably, two patients did not respond to the treatment, and in one patient, after initial partial response, new lesion was recorded. In untreated skin CF samples (n = 3), we observed numerous p53+ keratinocytes, similar to those observed in invasive SCC samples (53.56 ± 8.79 and 74.34 ± 22.05, respectively; P = 0.2). After treatment, we observed a v...Continue Reading

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Citations

Feb 27, 2020·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Kerry M HansonChristopher J Bardeen

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