Clinical Utility of the 40-Gene Expression Profile (40-GEP) Test for Improved Patient Management Decisions and Disease-Related Outcomes when Combined with Current Clinicopathological Risk Factors for Cutaneous Squamous Cell Carcinoma (cSCC): Case Series

Abstract

Introduction: While improvements have been made to risk assessment of cutaneous squamous cell carcinoma (cSCC) patients, there is a critical need for a uniform and more precise stratification system of their care. To address this unmet clinical need, a prognostic 40-gene expression profile (40-GEP) test has recently been developed and independently validated to show improved stratification of metastatic risk in high-risk cSCC patients compared with current staging systems. Methods: Two cSCC cases, both male with similar patient profiles and the same staging status across two different staging systems, yet with opposing outcomes, were chosen for retrospective review of their primary biopsy using the 40-GEP test.Results: Case 1 declined further treatment, even when presented with evidence of a small focus of cSCC found in the last layer of nonmarginal tissue obtained from Mohs micrographic surgery (MMS). Case 1 remained recurrence free, and retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 1 result (low likelihood of metastasis). Case 2, even with subsequent clearing of the primary cSCC with MMS, noted another metastatic cSCC 3 months later. Case 2, after multimodal adjuvant treatments, died due to disease progression. Retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 2B result (high likelihood of metastasis). Conclusions: The cases discussed highlight the utility in 40-GEP to provide additional information to guide treatment decisions and improve outcomes. Integrating novel molecular prognostication with traditional clinicopathological risk factors can improve stratification of high-risk cSCC patients and may inform selection of risk-appropriate treatment and surveillance strategies.

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions—Precision Dermatology

“…Overall, the risk of metastasis is less than half of that for the general study population for class 1 patients. A risk of 20% aligns with that of highrisk staging (BWH T2b and T3) for class 2A patients, and a risk of greater than 50% for class 2B patients is significantly higher than the risk of less than 7% for patients with class 1 results [82][83][84][85][86][87][88][89][90][91][92].…”

“…For example, some of the cutaneous SCC patients who were initially classified as low risk developed metastatic disease. In addition, other patients with cutaneous SCC who are classified as high-risk do not develop metastases [82][83][84][85][86][87][88][89][90][91][92].…”

“…A 40-GEP test has been developed to improve identification of individuals with primary cutaneous SCC who have a high risk of subsequently developing metastatic disease and to guide the decisions made by physicians regarding the possible performance of sentinel lymph node biopsy, potential management (such as radiation, chemotherapy, or immunotherapy), and follow-up intervals (ranging from every 3 to 6 to 12 months). The test can be used for a cutaneous SCC patient with one or more risk factors (Table 2) [82,[85][86][87][88][89][90][91][92]. Indeed, when it is used in combination with traditional risk factors, the result provides additional risk prediction of metastasis and death for the patient [82][83][84][85][86][87][88][89][90][91][92].…”

“…The test can be used for a cutaneous SCC patient with one or more risk factors (Table 2) [82,[85][86][87][88][89][90][91][92]. Indeed, when it is used in combination with traditional risk factors, the result provides additional risk prediction of metastasis and death for the patient [82][83][84][85][86][87][88][89][90][91][92].…”

“…RNA is extracted after macrodissection of the cutaneous SCC tumor tissue (including tumor stroma) from the formalin-fixed, paraffin-embedded tissue biopsy specimen. Subsequently, qRT-PCR is used to generate complementary DNA so that the expression of the 40 genes can be quantified and the tumor's risk for metastasis can be classified [82][83][84][85][86][87][88][89][90][91][92].…”