Non-Invasive Diagnosis of Sun Damaged Skin: Actinic Keratosis Vs Squamous Cell Carcinoma
May 2023 | Volume 22 | Issue 5 | 440 | Copyright © May 2023
Published online April 19, 2023
Mandy Majidian MD,a,b,e, Jane Anderson BSA,b,d, James A Rock MS,c, Rizi Ai PhD,c, John W. Whitaker PhD,c, Michael D. Howell phD,c, Ronald L. Moy MD,b
aTulane University School of Medicine, New Orleans, LA
bResearch Department, Moy-Fincher-Chipps Facial Plastics & Dermatology, Beverly Hills, CA
cDermTech Inc., La Jolla, CA
dThe University of Texas Health Science Center San Antonio, San Antonio, TX
eKaiser Permanente Los Angeles Medical Center, Los Angeles, CA
Abstract
Importance: Actinic keratosis (AK) is a premalignant lesion that has a1% to 10% potential of progression to squamous cell carcinoma (SCC), but it is not possible to determine which lesions are at higher risk.
Objective: This study examined the epidermal genetic profiles of actinic keratosis and SCC through non-invasive techniques seeking to develop a biopsy-free method for AK monitoring and aid in the early diagnosis of developing SCC.
Design: Ribonucleic acid (RNA) was collected from adhesive tape strips and gene expression levels were measured. A threshold fold change >2 and adjusted P-value <0.05 were used to determine differentially expressed genes.
Setting: Single center dermatology clinic.
Participants: Patients who presented to the clinic with lesions suspicious of non-melanoma skin cancer that had never been previously biopsied.
Main Outcome and Measure: RNA was extracted via non-invasive biopsy and sequenced. Low quality samples were filtered out and the remaining samples underwent differential gene expression analysis by DESeq2 in R package. A threshold of fold change
>2 and adjusted P-value <0.05 was used for determination of differentially expressed genes. The differentially expressed genes that overlapped between the corrected and uncorrected groups were the most significant for analysis.
Results: From 47 lesions, 6 significant differentially expressed genes were found between AK and SCC, and 25 significant differentially expressed genes between in-situ SCC and invasive SCC. Individual samples showed similarities based on diagnosis, suggesting mutations were specific to the disease and not the individual.
Conclusions and Relevance: These findings highlight which genes may play a role in AK progression to SCC. The genomic differences between in-situ and invasive squamous cell carcinoma open an opportunity for early diagnosis of squamous cell carcinoma and risk prediction of actinic keratosis.
J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7097
Majidian M, Anderson J, Rock JA, et al. Non-Invasive Diagnosis of Sun Damaged Skin: Actinic Keratosis Versus Squamous Cell Carcinoma.
J Drugs Dermatol. 2023;22(5):440-444. doi:10.36849/JDD.7097
INTRODUCTION
Actinic keratosis (AK) is considered to be a pre-cancerous lesion arising in response to chronic exposure to sunlight. While there are many presentations of AK, it is often characterized as a scaly, erythematous papule, or plaque.1 Because of its pre-cancerous classification, treatment is encouraged, with options including photodynamic therapy, topical chemotherapy creams, curettage and desiccation and, most commonly, cryotherapy with liquid nitrogen.
It is estimated that 1% to 10% of AK will progress to squamous cell carcinoma (SCC), the second-most common cutaneous malignancy.2 There are multiple theories regarding the pathogenesis of AK and its potential for malignant transformation to SCC. While some consider that AK is, in fact, a type of SCC, the most commonly accepted theory is that AKs can progress to SCC with additional ultraviolet (UV) radiation.3
There is no reliable way to clinically or pathologically predict which AK will progress to SCC. Clinical assessments of severity have not correlated with the histologic findings. As a result, the current mainstay of treatment of AK and progression to SCC has been diligent monitoring and treatment of AK as they arise.4
