title: Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy.
abstract: BACKGROUND
  The field cancerization concept in photodamaged patients suggests that the entire sun-exposed surface of the skin has an increased risk for the development of (pre)-malignant lesions, mainly epithelial tumours. Topical photodynamic therapy (PDT) is a noninvasive therapeutic method for multiple actinic keratosis (AK) with excellent outcome.
  
  
  OBJECTIVE
  To evaluate the clinical, histological and immunohistochemical changes in human skin with field cancerization after multiple sessions of PDT with methyl-aminolaevulinate (MAL).
  
  
  METHODS
  Twenty-six patients with photodamaged skin and multiple AK on the face received three consecutive sessions of MAL-PDT with red light (37 J cm(-2)), 1 month apart. Biopsies before and 3 months after the last treatment session were taken from normal-appearing skin on the field-cancerized area. Immunohistochemical stainings were performed for TP-53, procollagen-I, metalloproteinase-1 (MMP-1) and tenascin-C (Tn-C).
  
  
  RESULTS
  All 26 patients completed the study. The global score for photodamage improved considerably in all patients (P < 0·001). The AK clearance rate was 89·5% at the end of the study. Two treatment sessions were as effective as three MAL-PDT sessions. A significant decrease in atypia grade and extent of keratinocyte atypia was observed histologically (P < 0·001). Also, a significant increase in collagen deposition (P = 0·001) and improvement of solar elastosis (P = 0·002) were noticed after PDT. However, immunohistochemistry showed only a trend for decreased TP-53 expression (not significant), increased procollagen-I and MMP-1 expressions (not significant) and an increased expression of Tn-C (P = 0·024).
  
  
  CONCLUSIONS
  Clinical and histological improvement in field cancerization after multiple sessions of MAL-PDT is proven. The decrease in severity and extent of keratinocyte atypia associated with a decreased expression of TP-53 suggest a reduced carcinogenic potential of the sun-damaged area. The significant increase of new collagen deposition and the reduction of solar elastosis explain the clinical improvement of photodamaged skin.
authors.affiliation: Department of Dermatology, Regensburg University Hospital, Regensburg, Germany. rolf-markus.szeimies@klinikum-vest.de
authors.forename: R M
authors.initials: RM
authors.lastname: Szeimies
authors.forename: L
authors.initials: L
authors.lastname: Torezan
authors.forename: A
authors.initials: A
authors.lastname: Niwa
authors.forename: N
authors.initials: N
authors.lastname: Valente
authors.forename: P
authors.initials: P
authors.lastname: Unger
authors.forename: E
authors.initials: E
authors.lastname: Kohl
authors.forename: S
authors.initials: S
authors.lastname: Schreml
authors.forename: P
authors.initials: P
authors.lastname: Babilas
authors.forename: S
authors.initials: S
authors.lastname: Karrer
authors.forename: C
authors.initials: C
authors.lastname: Festa-Neto
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002985:Clinical Protocols; D005153:Facial Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D055623:Keratosis, Actinic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009824:Ointments; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D015595:Skin Aging / Q000528:radiation effects*
chemical_list: D009824:Ointments; D017319:Photosensitizing Agents; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid