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The Prognostic Role of CD8+ T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score

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Pelé Pequeno Príncipe Research Institute, 1532 Silva Jardim, AV., Curitiba, PR 80250-200, Brazil
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Faculdades Pequeno Príncipe, 333 Iguaçu Av., Rebouças, Curitiba, PR 80230-902, Brazil
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Hospital Infantil Joana Gusmão, 152 Rui Barbosa St., Florianópolis, SC 88025-300, Brazil
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Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC), UFPR, 400 Agostinho Leão Jr. Av., Curitiba, PR 80030-110, Brazil
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Serviço de Anatomia Patológica, Hospital de Clínicas, Universidade Federal do Paraná, 181 General Carneiro, Alto da Glória, Curitiba, PR 80060-900, Brazil
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Departamento de Medicina, PUCPR, 1155 Imaculada Conceição St., Prado Velho, Curitiba, PR 80215-901, Brazil
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Oxford Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Build, Roosevelt Dr, Oxford OX3 7DQ, UK
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Hospital Pequeno Príncipe, 1070 Desembargador Motta Av., Curitiba, Paraná 80250-060, Brazil
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Ciência Laboratório Médico Ltda-Hospital Infantil Joana de Gusmão, 152 Rui Barbosa St., Florianópolis, SC 88025-300, Brazil
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Department of Oncology, University of Turin, San Luigi Hospital, regione Gonzole 10, Orbassano, 10043 Turin, Italy
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Institut de Pharmacologie Moléculaire et Cellulaire CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France
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Departamento de Saúde Coletiva, Federal University of Paraná, 280 Padre Camargo, Alto da Glória, Curitiba, PR 80060-240, Brazil
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Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(11), 1730; https://doi.org/10.3390/cancers11111730
Received: 21 September 2019 / Revised: 25 October 2019 / Accepted: 1 November 2019 / Published: 5 November 2019
(This article belongs to the Special Issue Adrenocortical Carcinoma)
Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8+) cytotoxic T lymphocytes (CD8+-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8+-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8+-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8+ T cell recognition may provide insights for future pre-clinical studies. View Full-Text
Keywords: adrenocortical carcinoma; histopathology; children; HLA; immune escape adrenocortical carcinoma; histopathology; children; HLA; immune escape
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Parise, I.Z.S.; Parise, G.A.; Noronha, L.; Surakhy, M.; Woiski, T.D.; Silva, D.B.; Costa, T. .-J.; Del-Valle, M.H.C.P.; Komechen, H.; Rosati, R.; Ribeiro, M.G.; Nascimento, M.L.; Souza, J.A.; Andrade, D.P.; Paraizo, M.M.; Galvão, M.M.R.; Barbosa, J.R.S.; Barbosa, M.L.; Custódio, G.C.; Figueiredo, M.M.O.; Fabro, A.L.M.R.; Bond, G.; Volante, M.; Lalli, E.; Figueiredo, B.C. The Prognostic Role of CD8+ T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score. Cancers 2019, 11, 1730.

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