Translational Research

The clinical course of actinic keratosis correlates with underlying molecular mechanisms

Article first published online: 11 Sep 2019
DOI: 10.1111/bjd.18338

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Summary

Background

Actinic keratoses ( AK s) are common premalignant skin lesions triggered by excessive ultraviolet exposure. The majority of AK s regress or persist, but some progress to squamous cell carcinomas. Biomarkers associated with their persistence, progression and regression have not been characterized.

Objectives

We performed skin biopsies in patients with extensive actinic damage to identify biomarkers that correlate with clinical progression and regression of AK s.

Methods

This was an observational study of a cohort of patients with extensive actinic damage. AK s were mapped on a clear plastic template in 26 patients at months 3, 6, 9 and 11. Biopsies were taken from randomly selected, predetermined AK s and were evaluated for p53, E‐cadherin, Snail, Slug and Twist. The study is registered at Clinicaltrials.gov: NCT 00027976.

Results

p53 exhibited greater expression in clinically apparent AK s (histological score 2·89 ± 1·45) than in regressed AK s (0·75 ± 0·96); P < 0·01. There was also significantly less membrane E‐cadherin, the lack of which is a marker of epithelial–mesenchymal transition, in clinically apparent AK s (1·89 ± 1·81) than in sun‐exposed skin (3·07 ± 1·75); P < 0·005. The E‐cadherin transcription repressors Snail, Slug and Twist were increased in AK s compared with sun‐exposed skin. A limitation of the study is that measurement of histological biomarkers was not a primary end point. In addition, patients were allowed to apply sunscreens.

Conclusions

At the molecular level, loss of E‐cadherin and an increase in p53 are linked to the dynamic interplay between the persistence, progression and regression of AK s.

What’s already known about this topic?

Actinic keratoses (AKs) are common dysplastic epidermal lesions that result from chronic and excessive ultraviolet exposure. Biomarkers associated with progression and regression of AK have not been characterized.

What does this study add?

Decreased E‐cadherin and increased p53, Snail, Slug and Twist (E‐cadherin transcription factors) were associated with progression from AK to nonmelanoma skin cancer.

What is the translational message?

Strategies targeting these molecules may be effective in reversing rising skin cancer rates. E‐cadherin, p53, Snail, Slug and Twist are potential biomarkers that may be used to assess the efficacy of existing chemopreventive agents.

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