Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma

Ashley Wysong; Jason G. Newman; Kyle R. Covington; Sarah J. Kurley; Sherrif F. Ibrahim; Aaron S. Farberg; Anna Bar; Nathan J. Cleaver; Ally Khan Somani; David Panther; David G. Brodland; John Zitelli; Jennifer Toyohara; Ian A. Maher; Yang Xia; Kristin Bibee; Robert Griego; Darrell S. Rigel; Kristen Meldi Plasseraud; Sarah Estrada; Lauren Meldi Sholl; Clare Johnson; Robert W. Cook; Chrysalyne D. Schmults; Sarah T. Arron

doi:10.1016/j.jaad.2020.04.088

Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma

Ashley Wysong, Jason G. Newman, Kyle R. Covington, Sarah J. Kurley, Sherrif F. Ibrahim, Aaron S. Farberg, Anna Bar, Nathan J. Cleaver, Ally Khan Somani, David Panther, David G. Brodland, John Zitelli, Jennifer Toyohara, Ian A. Maher, Yang Xia, Kristin Bibee, Robert Griego, Darrell S. Rigel, Kristen Meldi Plasseraud, Sarah EstradaLauren Meldi Sholl, Clare Johnson, Robert W. Cook, Chrysalyne D. Schmults, Sarah T. Arron

Dermatology

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis. 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: 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: 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: Potential understaging of cases could affect metastasis rate accuracy. Conclusion: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.

Original language	English (US)
Pages (from-to)	361-369
Number of pages	9
Journal	Journal of the American Academy of Dermatology
Volume	84
Issue number	2
DOIs	https://doi.org/10.1016/j.jaad.2020.04.088
State	Published - Feb 2021

Keywords

cutaneous squamous cell carcinoma
gene expression profile
metastasis
prognostication
risk

ASJC Scopus subject areas

Dermatology

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10.1016/j.jaad.2020.04.088

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Wysong, A., Newman, J. G., Covington, K. R., Kurley, S. J., Ibrahim, S. F., Farberg, A. S., Bar, A., Cleaver, N. J., Somani, A. K., Panther, D., Brodland, D. G., Zitelli, J., Toyohara, J., Maher, I. A., Xia, Y., Bibee, K., Griego, R., Rigel, D. S., Meldi Plasseraud, K., ... Arron, S. T. (2021). Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. Journal of the American Academy of Dermatology, 84(2), 361-369. https://doi.org/10.1016/j.jaad.2020.04.088

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 2021, 'Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma', Journal of the American Academy of Dermatology, vol. 84, no. 2, pp. 361-369. https://doi.org/10.1016/j.jaad.2020.04.088

@article{d8ddf1fc397d435ea754ec37ce2b3e8b,

title = "Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma",

abstract = "Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis. 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: 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: 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: Potential understaging of cases could affect metastasis rate accuracy. Conclusion: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.",

keywords = "cutaneous squamous cell carcinoma, gene expression profile, metastasis, prognostication, risk",

author = "Ashley Wysong and Newman, {Jason G.} and Covington, {Kyle R.} and Kurley, {Sarah J.} and Ibrahim, {Sherrif F.} and Farberg, {Aaron S.} and Anna Bar and Cleaver, {Nathan J.} and Somani, {Ally Khan} and David Panther and Brodland, {David G.} and John Zitelli and Jennifer Toyohara and Maher, {Ian A.} and Yang Xia and Kristin Bibee and Robert Griego and Rigel, {Darrell S.} and {Meldi Plasseraud}, Kristen and Sarah Estrada and Sholl, {Lauren Meldi} and Clare Johnson and Cook, {Robert W.} and Schmults, {Chrysalyne D.} and Arron, {Sarah T.}",

note = "Publisher Copyright: {\textcopyright} 2020 American Academy of Dermatology, Inc.",

year = "2021",

month = feb,

doi = "10.1016/j.jaad.2020.04.088",

language = "English (US)",

volume = "84",

pages = "361--369",

journal = "Journal of the American Academy of Dermatology",

issn = "0190-9622",

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TY - JOUR

T1 - Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma

AU - Wysong, Ashley

AU - Newman, Jason G.

AU - Covington, Kyle R.

AU - Kurley, Sarah J.

AU - Ibrahim, Sherrif F.

AU - Farberg, Aaron S.

AU - Bar, Anna

AU - Cleaver, Nathan J.

AU - Somani, Ally Khan

AU - Panther, David

AU - Brodland, David G.

AU - Zitelli, John

AU - Toyohara, Jennifer

AU - Maher, Ian A.

AU - Xia, Yang

AU - Bibee, Kristin

AU - Griego, Robert

AU - Rigel, Darrell S.

AU - Meldi Plasseraud, Kristen

AU - Estrada, Sarah

AU - Sholl, Lauren Meldi

AU - Johnson, Clare

AU - Cook, Robert W.

AU - Schmults, Chrysalyne D.

AU - Arron, Sarah T.

PY - 2021/2

Y1 - 2021/2

N2 - Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis. 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: 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: 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: Potential understaging of cases could affect metastasis rate accuracy. Conclusion: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.

AB - Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis. 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: 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: 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: Potential understaging of cases could affect metastasis rate accuracy. Conclusion: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.

KW - cutaneous squamous cell carcinoma

KW - gene expression profile

KW - metastasis

KW - prognostication

KW - risk

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JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

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Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma

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