Newborn Screening for the Detection of the TP53 R337H Variant and Surveillance for Early Diagnosis of Pediatric Adrenocortical Tumors: Lessons Learned and Way Forward
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Karina C. F. Tosin
1, 
Edith F. Legal
2,
Mara A. D. Pianovski
3,
Humberto C. Ibañez
2,
Gislaine Custódio
4,
Denise S. Carvalho
1,
Mirna M. O. Figueiredo
4,
Anselmo Hoffmann Filho
2,
Carmem M. C. M. Fiori
5,
Ana Luiza M. Rodrigues
3,
Rosiane G. Mello
2,6,
Karin R. P. Ogradowski
2,6,
Ivy Z. S. Parise
2,
Tatiana E. J. Costa
7,
Viviane S. Melanda
8,
Flora M. Watanabe
9,
Denise B. Silva
7,
Heloisa Komechen
2,4,
Henrique A. Laureano
2,
Edna K. Carboni
9,
Ana P. Kuczynski
9,
Gabriela C. F. Luiz
9,
Leniza Lima
10,
Tiago Tormen
10,
Viviane K. Q. Gerber
11,
Tania H. Anegawa
12,
Sylvio G. A. Avilla
9,
Renata B. Tenório
9,
Elaine L. Mendes
9,
Rayssa D. Fachin Donin
4,
Josiane Souza
9,
Vanessa N. Kozak
3,
Gisele S. Oliveira
3,
Deivid C. Souza
3,
Israel Gomy
6,9,
Vinicius B. Teixeira
2
,
Helena H. L. Borba
13,
Nilton Kiesel Filho
9,
Guilherme A. Parise
4,
Raul C. Ribeiro
14,* and
Bonald C. Figueiredo
1,2,4,6,*add
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1
Departamento de Saúde Coletiva, Federal University of Paraná, Rua Padre Camargo, 260, Centro, Curitiba 80.060-240, PR, Brazil
2
Instituto de Pesquisa Pelé Pequeno Príncipe, Silva Jardim, 1532, Curitiba 80.250-060, PR, Brazil
3
Oncologia Pediátrica, Hospital Erasto Gaertner, R. Dr. Ovande do Amaral, 201, Jardim das Américas, Curitiba 81.520-060, PR, Brazil
4
Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC-APACN), Avenida Agostinho Leão Jr., 400, Curitiba 80.030-110, PR, Brazil
5
Hospital do Câncer, UOPECCAN, R. Itaquatiaras, 769, Santo Onofre, Cascavel 85.806-300, PR, Brazil
6
Faculdades Pequeno Príncipe, Av. Iguaçu, 333, Rebouças, Curitiba 80.230-020, PR, Brazil
7
Hospital Infantil Joana de Gusmão, R. Rui Barbosa, 152, Agronômica, Florianópolis 88.025-301, SC, Brazil
8
Secretaria do Estado da Saúde do Paraná, R. Piquiri, 170, Rebouças, Curitiba 80.230-140, PR, Brazil
9
Hospital Pequeno Príncipe, Silva Jardim, 1532, Curitiba 80.250-060, PR, Brazil
10
Oncologia Pediátrica, Hospital de Clínicas da Universidade Federal do Paraná, R. Gen. Carneiro, 181, Alto da Glória, Curitiba 80.060-900, PR, Brazil
11
Departamento de Enfermagem, Universidade Estadual do Centro-Oeste, UNICENTRO, Rua Padre, R. Salvatore Renna, 875-Santa Cruz, Guarapuava 85.015-430, PR, Brazil
12
Oncologia Pediátrica, Campus Universitário, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid—Pr 445 Km 380, Londrina 86.057-970, PR, Brazil
13
Departamento de Ciências Farmacêuticas, Federal University of Paraná, Av. Prefeito Lothário Meissner, 632-Jardim Botanico, Curitiba 80.210-170, PR, Brazil
14
Leukemia and Lymphoma Division, Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
*
Authors to whom correspondence should be addressed.
Cancers 2021, 13(23), 6111; https://doi.org/10.3390/cancers13236111
Submission received: 31 August 2021
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Revised: 30 October 2021
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Accepted: 1 November 2021
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Published: 3 December 2021
(This article belongs to the Special Issue New Insights in the Genetics and Genomics of Adrenocortical Tumors and Pheochromocytomas)
Simple Summary
Adrenocortical tumor (ACT) is rare in children and fatal if not detected early. Children who inherit a mutation of the TP53 gene tend to develop ACT early in life. In the 1990s, scientists revealed that a TP53 variant (R337H) was frequent in South Brazil. Therefore, the incidence of ACT in children is 20 times higher in this region than in other countries. We reviewed the records of 16 children with ACT treated in a pediatric hospital in Parana state (southern Brazil) and 134 children registered in the state public registry data. We found a high number of cases with advanced disease, leading to an unacceptable number of deaths. These observations contradict newborn R337H screening and surveillance data, showing that surgical intervention in early cases of ACT is associated with a 100% cure. Newborn screening/surveillance should be implemented in regions with a high frequency of the R337H variant.
Abstract
The incidence of pediatric adrenocortical tumors (ACT) is high in southern Brazil due to the founder TP53 R337H variant. Neonatal screening/surveillance (NSS) for this variant resulted in early ACT detection and improved outcomes. The medical records of children with ACT who did not participate in newborn screening (non-NSS) were reviewed (2012–2018). We compared known prognostic factors between the NSS and non-NSS cohorts and estimated surveillance and treatment costs. Of the 16 non-NSS children with ACT carrying the R337H variant, the disease stages I, II, III, and IV were observed in five, five, one, and five children, respectively. The tumor weight ranged from 22 to 608 g. The 11 NSS children with ACT all had disease stage I and were alive. The median tumor weight, age of diagnosis, and interval between symptoms and diagnosis were 21 g, 1.9 years, and two weeks, respectively, for the NSS cohort and 210 g, 5.2 years, and 15 weeks, respectively, for the non-NSS cohort. The estimated surveillance/screening cost per year of life saved is US$623/patient. NSS is critical for improving the outcome of pediatric ACT in this region. Hence, we strongly advocate for the inclusion of R337H in the state-mandated universal screening and surveillance.
