Bridging the Gap: Integrating Gene Expression Profiling into Clinical Practice

June 2021 | Volume 20 | Issue 6 | Supplement Individual Articles | s4 | Copyright © June 2021

Published online May 11, 2021

Aaron S. Farberg MD,a Teo Soleymani MD,b Desiree Ratner MDc

aDivision of Dermatology, Baylor University Medical Center, Dallas, TX; College of Medicine, Texas A&M University, Bryan, TX
bDivision of Dermatology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
cDepartment of Dermatology, NYU Langone Health, New York, NY

Clinicians who treat patients with cutaneous squamous cell carcinoma (CSCC) face a unique set of management challenges. While the aim is to identify biologically aggressive tumors at earlier stages of progression and tumors that may be more advanced but pose lower than predicted risk, prognostication is not always accurate. Furthermore, even after careful clinical and histopathologic risk stratification, there remains significant variability in managing patients with high-risk CSCC. To address this challenge, experts are evaluating tools designed to improve risk stratification of these patients as discussed by the authors of this article.

Gene expression profile (GEP) testing has been shown, in combination with established clinical and histologic factors, to refine risk prediction for outcomes of interest for multiple diseases.1 The recently developed and validated 40-GEP test for CSCC is the first clinically available GEP test used to predict the risk of nodal and distant metastasis and should only be considered for use in tumors with one or more high-risk factors.2 The probability of nodal or distant CSCC metastasis varies based on established clinicopathologic risk factors, which current management algorithms use to provide recommendations appropriate for each individual patient. GEP testing for CSCC has the ability to provide clinicians with objective data from the primary tumor that can augment existing risk stratification, which could be an important and beneficial advance in patient care.

CSCC patients who ultimately experience poor outcomes have a variety of initial presentations and start their clinical journeys in diverse practice settings across the country. The clinician performing the initial biopsy may not be responsible for managing the advanced sequelae of that same lesion years after its diagnosis and primary treatment, and their initial assessment of patient risk may or may not be accurate. This article illustrates how collective decision making can help bridge existing gaps in current clinical guidelines to develop a plan of care for high-risk patients whose level of risk is unknown. The information gained from GEP testing provides more precise risk stratification and allows patients at highest risk of poor outcomes to be managed more aggressively and followed more closely. Because of the wide variety of risk-assessment approaches, treatment settings, and specialties involved in treating CSCC, it is unlikely that there will be a standardized approach to initiating GEP testing, but rather that a nuanced assessment of each patient’s individual risk profile will be required to arrive at a decision. Furthermore, as the authors emphasize, GEP test results should be interpreted in the context of each patient’s individual clinicopathologic risk factors to assess the appropriateness of nodal evaluation, the need for adjuvant radiation therapy, the frequency of follow-up intervals, and the level of required surveillance.


1. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121.
2. Wysong A, Newman JG, Covington KR, et al. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2021;84(2):361-369.