Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy

Br J Dermatol. 2012 Jul;167(1):150-9. doi: 10.1111/j.1365-2133.2012.10887.x. Epub 2012 Jun 1.

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.

Objectives: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Aged
  • Aged, 80 and over
  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / analogs & derivatives*
  • Clinical Protocols
  • Facial Neoplasms / drug therapy*
  • Female
  • Humans
  • Immunohistochemistry
  • Keratosis, Actinic / drug therapy*
  • Male
  • Middle Aged
  • Ointments
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage*
  • Skin Aging / radiation effects*

Substances

  • Ointments
  • Photosensitizing Agents
  • methyl 5-aminolevulinate
  • Aminolevulinic Acid