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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Authors

  • Ivy Zortéa S Parise
  • Guilherme A Parise
  • Lúcia Noronha
  • Mirvat Surakhy
  • Thiago Demetrius Woiski
  • Denise B Silva
  • Tatiana Ei-Jaick B Costa
  • Maria Helena C P Del-Valle
  • Heloisa Komechen
  • Roberto Rosati
  • Melyssa Grignet Ribeiro
  • Marilza Leal Nascimento
  • José Antônio de Souza
  • Diancarlos P Andrade
  • Mariana M Paraizo
  • Marjorana Martini R Galvão
  • José Renato S Barbosa
  • Miriam Lacerda Barbosa
  • Gislaine C Custódio
  • Mirna M O Figueiredo
  • Ana Luiza M R Fabro
  • Marco Volante
  • Enzo Lalli
  • Bonald C Figueiredo

Colleges, School and Institutes

External organisations

  • Hospital Infantil Joana Gusmão, 152 Rui Barbosa St., Florianópolis, SC 88025-300, Brazil.
  • Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC), UFPR, 400 Agostinho Leão Jr. Av., Curitiba, PR 80030-110, Brazil.
  • Departamento de Medicina, PUCPR, 1155 Imaculada Conceição St., Prado Velho, Curitiba, PR 80215-901, Brazil.
  • 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.
  • Hospital Pequeno Príncipe, 1070 Desembargador Motta Av., Curitiba, Paraná 80250-060, Brazil.
  • Faculdades Pequeno Príncipe, 333 Iguaçu Av., Rebouças, Curitiba, PR 80230-902, Brazil.
  • Serviço de Anatomia Patológica, Hospital de Clínicas, Universidade Federal do Paraná, 181 General Carneiro, Alto da Glória, Curitiba, PR 80060-900, Brazil.
  • Ciência Laboratório Médico Ltda-Hospital Infantil Joana de Gusmão, 152 Rui Barbosa St., Florianópolis, SC 88025-300, Brazil.
  • Department of Oncology, University of Turin, San Luigi Hospital, regione Gonzole 10, Orbassano, 10043 Turin, Italy.
  • Institut de Pharmacologie Moléculaire et Cellulaire CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
  • Departamento de Saúde Coletiva, Federal University of Paraná, 280 Padre Camargo, Alto da Glória, Curitiba, PR 80060-240, Brazil.

Abstract

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.

Details

Original languageEnglish
JournalCancers
Volume11
Issue number11
Publication statusPublished - 5 Nov 2019