Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Carcinoma, Squamous Cell
/ diagnosis
Female
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Staging
/ methods
Predictive Value of Tests
Prognosis
Prospective Studies
Risk Assessment
/ methods
Skin
/ pathology
Skin Neoplasms
/ diagnosis
Survival Rate
cutaneous squamous cell carcinoma
gene expression profile
metastasis
prognostication
risk
Journal
Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
20
01
2020
revised:
22
03
2020
accepted:
15
04
2020
pubmed:
29
4
2020
medline:
30
7
2021
entrez:
29
4
2020
Statut:
ppublish
Résumé
Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis. To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management. Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature was developed using a discovery cohort (n = 202) and validated in a separate, nonoverlapping, independent cohort (n = 324). A prognostic 40-GEP test was developed and validated, stratifying patients with high-risk cSCC into classes based on metastasis risk: class 1 (low risk), class 2A (high risk), and class 2B (highest risk). For the validation cohort, 3-year metastasis-free survival rates were 91.4%, 80.6%, and 44.0%, respectively. A positive predictive value of 60% was achieved for the highest-risk group (class 2B), an improvement over staging systems, and negative predictive value, sensitivity, and specificity were comparable to staging systems. Potential understaging of cases could affect metastasis rate accuracy. The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.
Sections du résumé
BACKGROUND
BACKGROUND
Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis.
OBJECTIVE
OBJECTIVE
To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management.
METHODS
METHODS
Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature was developed using a discovery cohort (n = 202) and validated in a separate, nonoverlapping, independent cohort (n = 324).
RESULTS
RESULTS
A prognostic 40-GEP test was developed and validated, stratifying patients with high-risk cSCC into classes based on metastasis risk: class 1 (low risk), class 2A (high risk), and class 2B (highest risk). For the validation cohort, 3-year metastasis-free survival rates were 91.4%, 80.6%, and 44.0%, respectively. A positive predictive value of 60% was achieved for the highest-risk group (class 2B), an improvement over staging systems, and negative predictive value, sensitivity, and specificity were comparable to staging systems.
LIMITATIONS
CONCLUSIONS
Potential understaging of cases could affect metastasis rate accuracy.
CONCLUSION
CONCLUSIONS
The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.
Identifiants
pubmed: 32344066
pii: S0190-9622(20)30704-0
doi: 10.1016/j.jaad.2020.04.088
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Multicenter Study
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
361-369Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2020 American Academy of Dermatology, Inc. All rights reserved.