QHow to navigate GEP testing for SCC

Aaron Farberg, MD

Aaron Farberg, MD

Dermatologist and Mohs Surgeon
Baylor University Medical Center
Dallas, TX

Gene expression profile (GEP) tests have been developed to augment traditional clinicopathologic assessments in multiple malignancies including breast, prostate, cutaneous melanoma, lung, and colorectal cancer. A prognostic 40 gene expression profile test with three progressing gradients of risk (e.g., Class1, Class2A, and Class2B) was developed and validated as a tool to predict metastatic risk of high(er)-risk cSCC and assist in guiding management regarding sentinel lymph node assessment, follow-up duration/frequency, and adjuvant radiation therapy (to name a few).1,2  

Multivariate analyses have demonstrated that 40-GEP Class2A cSCC carry a similar risk of metastasis as BWH T2b/T3 (~20% risk) and, based on risk-threshold of existing recommendations, may benefit from radiologic imaging (PET/CT). 1 Furthermore, recent expert consensus has determined that the 40-GEP Class2A or 2B may augment AJCC8/BWH-based decision-making when counseling patients regarding sentinel lymph node biopsy.  

Given the different 40-GEP Classes also indicate different levels of metastatic risk (e.g., Class1: <7%; Class2A: ~20%; Class2B >50%), expert consensus also determined 40-GEP status can assist in determining follow-up frequency/intensity, especially within the first two-year period when cSCC metastatic risk is highest. 2 For example, patients with low metastatic risk (e.g., Class1) may only need a clinical follow-up while a Class2B patient may require a twice-yearly evaluation with radiologic assessment. 

While not explicitly designed to guide adjuvant radiation therapy management, studies have determined that a 40-GEP Class2A result (and AJCC T3/T4 or BWH T2b/T3 stage) were up to 5.8 times more likely to metastasize, while similarly staged tumors with a 40-GEP Class2B result were 15 times more likely to metastasize. 1 This individualized prognostic knowledge may assist in determining risk-benefit analysis in determining treatment plan and should be further explored in future studies. 

GEP testing has the ability to further personalize patient care, minimizing risk while potentially maximizing safety and efficacy of management.  


  1. Wysong A, Newman JG, Covington KR, Kurley SJ, Ibrahim SF, Farberg AS, Bar A, Cleaver NJ, Somani AK, Panther D, Brodland DG, Zitelli J, Toyohara J, Maher IA, Xia Y, Bibee K, Griego R, Rigel DS, Meldi Plasseraud K, Estrada S, Sholl LM, Johnson C, Cook RW, Schmults CD, Arron ST. 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 Feb;84(2):361-369. doi: 10.1016/j.jaad.2020.04.088. Epub 2020 Apr 25. Erratum in: J Am Acad Dermatol. 2021 Jun;84(6):1796. PMID: 32344066. 
  2. Arron ST, Blalock TW, Guenther JM, Hyams DM, Ibrahim SF, Koyfman SA, Wysong A. Clinical Considerations for Integrating Gene Expression Profiling into Cutaneous Squamous Cell Carcinoma Management. J Drugs Dermatol. 2021 Jun 1;20(6):5s-s11. doi: 10.36849/JDD.2021.6068. PMID: 34076385.