Enhanced Metastatic Risk Assessment in Cutaneous Squamous Cell Carcinoma with the 40-Gene Expression Profile Test

Abstract

Aim: To clinically validate the 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma patients and evaluate coupling the test with individual clinicopathologic risk factor-based assessment methods. Patients & methods: In a 33-site study, primary tumors with known patient outcomes were assessed under clinical testing conditions (n = 420). The 40-GEP results were integrated with clinicopathologic risk factors. Kaplan–Meier and Cox regression analyses were performed for metastasis. Results: The 40-GEP test demonstrated significant prognostic value. Risk classification was improved via integration of 40-GEP results with clinicopathologic risk factor-based assessment, with metastasis rates near the general cutaneous squamous cell carcinoma population for Class 1 and ≥50% for Class 2B. Conclusion: Combining molecular profiling with clinicopathologic risk factor assessment enhances stratification of cutaneous squamous cell carcinoma patients and may inform decision-making for risk-appropriate management strategies.

Gene expression profiling for metastatic risk in head and neck cutaneous squamous cell carcinoma

“…Previously, we demonstrated that molecular profiling using the clinically validated 40-GEP test provided significant independent prognostic value for metastatic risk assessment in a cohort of cSCC patients (n = 420), while also complementing clinicopathologic risk assessment methods. 23 Here, we focus on the H&N subset (n = 278, 66.2%) from that cohort to demonstrate the 40-GEP test can also be a significant independent and complementary prognostic tool for determining metastatic risk in cSCC-HN.…”

“…Informed consent was obtained from study participants as required. Tissue and data for this cohort are a subset (66.2%) of a previously reported high-risk cSCC cohort studied for clinical validation of the 40-GEP test, 23 and inclusion/exclusion criteria have been previously described. 22 Importantly, tumors from cSCC-HN (n = 87) that were used during the discovery of the 40-GEP 22 were not included in the abovementioned clinical validation study, 23 nor were they part of the current cSCC-HN cohort study.…”

“…Tissue and data for this cohort are a subset (66.2%) of a previously reported high-risk cSCC cohort studied for clinical validation of the 40-GEP test, 23 and inclusion/exclusion criteria have been previously described. 22 Importantly, tumors from cSCC-HN (n = 87) that were used during the discovery of the 40-GEP 22 were not included in the abovementioned clinical validation study, 23 nor were they part of the current cSCC-HN cohort study. Tissue samples were analyzed via clinical standard operating procedures for the 40-GEP test, and patient data were monitored via centralized review of pathology reports and medical records as previously described.…”

“…[19][20][21] However, the accuracy of these systems for predicting metastatic risk in cSCC is low (positive predictive value [PPV] of 33% and 35% for AJCC8 [T3/T4] and BWH [T2b/T3], respectively) relative to what has recently been reported for a prognostic 40-gene expression profile (40-GEP) test (PPV, 60% for Class 2B). 22,23 Of importance, the AJCC8 staging system addresses cSCC of only the H&N region, whereas previous editions addressed cSCC in other anatomical sites as well. 20,24 Having a prognostic tool, such as the 40…”

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

“…The advancement of gene expression profiling signatures for use in clinical management make them a powerful prognostic tool, when complementing staging, for many other tumor types [15][16][17][18][19]. A recent publication from Ibrahim et al [20] demonstrated how combining both clinicopathologic…”