Genetic change in actinic keratoses

Area of Science:

• Dermatology
• Oncology
• Cancer Genetics

Background:

• Actinic keratoses (AKs) are common skin lesions with potential to progress to squamous cell carcinoma (SCC).
• AKs are characterized by epidermal dysplasia and a high rate of spontaneous regression.
• Despite a generally benign clinical course, AKs display significant genetic instability.

Purpose of the Study:

• To investigate the frequency and patterns of genetic alterations, specifically loss of heterozygosity (LOH) and p53 mutations, in actinic keratoses.
• To explore the relationship between genetic changes, histological dysplasia, and the expression of p21WAF1/CIP1.
• To compare the genetic landscape of AKs with that of invasive squamous cell carcinoma.

Main Methods:

• Analysis of loss of heterozygosity (LOH) at multiple genetic loci in AK lesions.
• Assessment of p53 mutation status in AKs.
• Evaluation of p21WAF1/CIP1 expression patterns and correlation with genetic alterations and cell proliferation.

Main Results:

• A high frequency of LOH was observed in AKs, with a median loss of four loci and frequent p53 mutations.
• Specific chromosomal regions (3p, 9p, 9q, 13q, 17p, 17q) showed common allele loss, correlating with the degree of dysplasia.
• Disturbed p21WAF1/CIP1 expression was associated with allele loss and increased cell proliferation, potentially representing an early event independent of p53 status.

Conclusions:

• Actinic keratoses harbor substantial genetic instability, including frequent LOH and p53 mutations, exceeding that seen in invasive SCC.
• The observed genetic alterations and p21WAF1/CIP1 expression changes suggest complex early events in AKs.
• The relationship between genetic changes and clinical behavior in non-melanoma skin cancer is not linear.