title: Ingenol mebutate in actinic keratosis: a clinical, videodermoscopic and immunohistochemical study.
abstract: BACKGROUND
  Actinic keratosis (AK) is a cutaneous intraepithelial neoplasm that typically develops on sun-damaged skin. The incidence of AK is increasing worldwide, and it is accepted as the most frequent pre-malignant lesion in humans.
  
  
  OBJECTIVE
  To demonstrate that ingenol mebutate gel is effective in the treatment of actinic keratoses because of its clinical, dermoscopic, capillaroscopic, histopathological and immunohistochemical treatment outcomes.
  
  
  METHODS
  Sixty individuals with multiple non-hypertrophic AKs were enrolled into this non-randomized, open-label, prospective, trial. Acquisition of clinical, dermoscopic and capillaroscopic images at baseline (T0), immediately after treatment on 3rd(trunk and/or extremities) or 4th(scalp and/or face) day (T1), 14 days after the end of the treatment (T2) and at 60 days (T3). A subgroup of 20 patients received a cutaneous biopsy both at baseline and at T3 for histological and immunohistochemical evaluation.
  
  
  RESULTS
  Clinical improvement was observed in 100% of cases: total clearance in 41 patients (68.3%); partial clearance in 19 patients (32.7%). After treatment, dermoscopic improvement of all non-pigmented and pigmented AK lesions was observed. Most of the dermoscopic features disappeared with treatment. Total disappearance of specific vascular structures or significant reduction in the number and calibre of new blood vessels was capillaroscopically observed in all patients analysed (P ≤ 0.001). The immunohistochemical expression of p63 (P = 0.002), Ki-67 (P = 0.015) and VEGF (P = 0.016) significantly decreased.
  
  
  CONCLUSIONS
  The clinical efficacy of ingenol mebutate on AKs is confirmed by its effect on angiogenesis, stem cell activity and cell proliferation in vivo.
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Bobyr
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Campanati
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Consales
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Martina
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Molinelli
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Diotallevi
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Brisigotti
authors.affiliation: Institute of Pathological Anatomy and Histopathology, Polytechnic University Marche, Ancona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Giangiacomi
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ganzetti
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: K
authors.initials: K
authors.lastname: Giuliodori
authors.affiliation: Dermatological Unit, Department of Clinical and Molecular Sciences, Polytehnic Marche University, Ancona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Offidani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D046169:Dermoscopy / Q000379:methods*; D004224:Diterpenes / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: C486592:3-ingenyl angelate; D004224:Diterpenes