Stefan Kraft1, Maria-Teresa Fernandez-Figueras2, Nina A Richarz3, Keith T Flaherty4, Mai P Hoang5. 1. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 2. Department of Pathology, Hospital Universitari Germans Trias i Pujol, Univeristat Autònoma de Barcelona, Badalona, Barcelona, Spain. 3. Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Univeristat Autònoma de Barcelona, Badalona, Barcelona, Spain. 4. Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 5. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: mhoang@mgh.harvard.edu.
Abstract
BACKGROUND: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. METHODS: We correlated PDL1, p53, and Ki-67 expression with CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. RESULTS: Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis. According to linear regression analysis, tumoral PDL1 expression correlated with thickness (P = .0041); p53 expression (P = .019); Ki-67 proliferation index (P = .0018); and tumoral CD8 (P = .0084), stromal CD8 (P < .0001), and FoxP3 (P < .0001) T-cell counts. According to univariate analyses, PDL1 expression of 25% or higher correlated with shorter progression-free survival (P < .0001) and melanoma-specific survival (P = .034). According to multivariate analyses, PDL1 expression of 25% or more (P = .026) and mixed histology (P = .039) independently predicted shorter progression-free survival, and presence of lymphovascular invasion predicted shorter overall survival (P = .018). LIMITATIONS: Small study size. CONCLUSION: Tumoral and stromal CD8+ and FoxP3+ lymphocyte counts correlated with tumoral PDL1 expression, which is supportive of an adaptive immune response. PDL1 expression in desmoplastic melanoma was associated with tumor aggressiveness and progression. Although PDL1 expression is typically low in melanoma, its frequency and level of expression in desmoplastic melanoma may identify a subset of melanomas that are likely to respond to immunotherapy.
BACKGROUND: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. METHODS: We correlated PDL1, p53, and Ki-67 expression with CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. RESULTS:TumoralPDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis. According to linear regression analysis, tumoralPDL1 expression correlated with thickness (P = .0041); p53 expression (P = .019); Ki-67 proliferation index (P = .0018); and tumoralCD8 (P = .0084), stromal CD8 (P < .0001), and FoxP3 (P < .0001) T-cell counts. According to univariate analyses, PDL1 expression of 25% or higher correlated with shorter progression-free survival (P < .0001) and melanoma-specific survival (P = .034). According to multivariate analyses, PDL1 expression of 25% or more (P = .026) and mixed histology (P = .039) independently predicted shorter progression-free survival, and presence of lymphovascular invasion predicted shorter overall survival (P = .018). LIMITATIONS: Small study size. CONCLUSION:Tumoral and stromal CD8+ and FoxP3+ lymphocyte counts correlated with tumoralPDL1 expression, which is supportive of an adaptive immune response. PDL1 expression in desmoplastic melanoma was associated with tumor aggressiveness and progression. Although PDL1 expression is typically low in melanoma, its frequency and level of expression in desmoplastic melanoma may identify a subset of melanomas that are likely to respond to immunotherapy.
Authors: Anne M Stowman; Alexandra W Hickman; Ileana S Mauldin; Adela Mahmutovic; Alejandro A Gru; Craig L Slingluff Journal: Melanoma Res Date: 2018-06 Impact factor: 3.599
Authors: Deborah Blythe Doroshow; Sheena Bhalla; Mary Beth Beasley; Lynette M Sholl; Keith M Kerr; Sacha Gnjatic; Ignacio I Wistuba; David L Rimm; Ming Sound Tsao; Fred R Hirsch Journal: Nat Rev Clin Oncol Date: 2021-02-12 Impact factor: 66.675
Authors: Fernando M Simabuco; Mirian G Morale; Isadora C B Pavan; Ana P Morelli; Fernando R Silva; Rodrigo E Tamura Journal: Oncotarget Date: 2018-05-04
Authors: Alexander Thiem; Sonja Hesbacher; Hermann Kneitz; Teresa di Primio; Markus V Heppt; Heike M Hermanns; Matthias Goebeler; Svenja Meierjohann; Roland Houben; David Schrama Journal: J Exp Clin Cancer Res Date: 2019-09-11