Ashley Wysong1, Jason G Newman2, Kyle R Covington3, Sarah J Kurley3, Sherrif F Ibrahim4, Aaron S Farberg5, Anna Bar6, Nathan J Cleaver7, Ally-Khan Somani8, David Panther9, David G Brodland9, John Zitelli9, Jennifer Toyohara10, Ian A Maher11, Yang Xia12, Kristin Bibee13, Robert Griego14, Darrell S Rigel15, Kristen Meldi Plasseraud3, Sarah Estrada16, Lauren Meldi Sholl17, Clare Johnson17, Robert W Cook18, Chrysalyne D Schmults19, Sarah T Arron20. 1. University of Nebraska Medical Center, Omaha, Nebraska. 2. University of Pennsylvania, Philadelphia, Pennsylvania. 3. Castle Biosciences, Inc, Friendswood, Texas. 4. University of Rochester, Rochester, New York. 5. Icahn School of Medicine at Mount Sinai, New York, New York; Arkansas Dermatology Skin Cancer Center, Little Rock, Arkansas. 6. Oregon Health & Science University, Portland, Oregon. 7. Cleaver Dermatology, Kirksville, Missouri. 8. Indiana University School of Medicine, Indianapolis, Indiana. 9. Zitelli and Brodland, P.C. Skin Cancer Center, Pittsburgh, Pennsylvania. 10. Adult & Pediatric Dermatology, Concord, Massachusetts. 11. University of Minnesota, Minneapolis, Minnesota. 12. Brooke Army Medical Center, San Antonio, Texas. 13. University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 14. Skin Cancer Specialists, Ltd, Mesa, Arizona. 15. New York University School of Medicine, New York, New York. 16. Castle Biosciences, Inc, Phoenix, Arizona; Affiliated Dermatology, Scottsdale, Arizona. 17. Castle Biosciences, Inc, Phoenix, Arizona. 18. Castle Biosciences, Inc, Friendswood, Texas. Electronic address: rcook@castlebiosciences.com. 19. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 20. University of California San Francisco, San Francisco, California. Electronic address: sarah.arron@ucsf.edu.
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.
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.
Authors: Sherri Borman; Jeff Wilkinson; Lauren Meldi-Sholl; Clare Johnson; Kelsey Carter; Kyle R Covington; Alison L Fitzgerald; Sarah J Kurley; Aaron S Farberg; Matthew S Goldberg; Federico A Monzon; Kristen Oelschlager; Robert W Cook Journal: Diagn Pathol Date: 2022-02-25 Impact factor: 2.644
Authors: Sarah T Arron; Ashley Wysong; Mary A Hall; Christine N Bailey; Kyle R Covington; Sarah J Kurley; Matthew S Goldberg; Julia M Kasprzak; Ally-Khan Somani; Sherrif F Ibrahim; David G Brodland; Nathan J Cleaver; Ian A Maher; Yang Xia; Shlomo A Koyfman; Jason G Newman Journal: Laryngoscope Investig Otolaryngol Date: 2022-01-06
Authors: Aaron S Farberg; Alison L Fitzgerald; Sherrif F Ibrahim; Stan N Tolkachjov; Teo Soleymani; Leah M Douglas; Sarah J Kurley; Sarah T Arron Journal: Dermatol Ther (Heidelb) Date: 2022-01-07
Authors: Ann W Silk; Christopher A Barker; Shailender Bhatia; Kathryn B Bollin; Sunandana Chandra; Zeynep Eroglu; Brian R Gastman; Kari L Kendra; Harriet Kluger; Evan J Lipson; Kathleen Madden; David M Miller; Paul Nghiem; Anna C Pavlick; Igor Puzanov; Guilherme Rabinowits; Emily S Ruiz; Vernon K Sondak; Edward A Tavss; Michael T Tetzlaff; Isaac Brownell Journal: J Immunother Cancer Date: 2022-07 Impact factor: 12.469
Authors: Ignazio Stanganelli; Francesco Spagnolo; Giuseppe Argenziano; Paolo A Ascierto; Franco Bassetto; Paolo Bossi; Vittorio Donato; Daniela Massi; Cesare Massone; Roberto Patuzzo; Giovanni Pellacani; Pietro Quaglino; Paola Queirolo; Iris Zalaudek; Giuseppe Palmieri Journal: Cancers (Basel) Date: 2022-01-13 Impact factor: 6.639