Pediatric oncologist investigated tumors of the adrenal gland cortex
Tumors of the adrenal gland cortex (ACT) mainly affect children in the first five years of life. They are considered rare in this age group, but their occurrence in the South and Southeast regions of Brazil is 18 times more frequent in childhood than in other countries. In the Campinas region, it affects one for every 270 newborns.
The high frequency is explained due to the hereditary germline mutation of the gene TP53. It is considered the guardian gene of the human genome. The mutation of this gene can be transmitted to future generations and predisposes to the development of adrenocortical tumor in childhood and other types of cancer in adults.
This is what pediatric oncologist Maria José Mastellaro points out in her doctoral thesis Adrenocortical tumors in childhood: impact of hormonal exposure and treatment on growth and development, current health status of long-term survivors, and familial susceptibility to cancer related to the germline mutation of the TP53 gene p.Arg337His, defended at the Faculty of Medical Sciences (FCM) at Unicamp.
"This mutation is exclusive to Brazil and was described in 2001. TP53 it is a founding gene that came at the time of the country's colonization. Around 90% of patients with TCA studied in 30 years of care at the Boldrini Children's Center were carriers of the hereditary mutation p.Arg337His of the gene TP53, which predisposes to familial cancer”, says Maria José.
The thesis was defended in the postgraduate program in Sciences, in the area of concentration in Pediatrics and the guidance was given by Professor Antônio de Azevedo Barros Filho, from the Department of Pediatrics at FCM. Co-guidance was provided by Raul Correa Ribeiro, physician at the International Outreach Program and Department of Oncology at St. Jude Children's Research Hospital, Memphis, TN, USA.
The search results yielded two articles: Assessment of growth and clinical signs of corticosteroid secretion facilitates early detection of adrenocortical tumors in childhood e The contribution of the TP53 R337H mutation to the cancer burden in Southern Brazil: Insights from the study of 55 families of children with adrenocortical tumors, published in Interdisciplinary International Journal of the American Cancer Society.
“In 1982, after joining the oncology internship at Boldrini, during my residency at the Department of Pediatrics at FCM, I could not have imagined that my first case of cancer in an eight-month-old baby would accompany me throughout my professional and academic career”, he reveals. Maria Jose.
103 patients with adrenal cortex tumors who were treated and monitored from 1982 to 2014 at the Centro Infantil Boldrini, in Campinas, SP, were eligible for the research. During this period, the researcher also followed 55 families of patients carrying the gene mutation TP53 and 55 families without the genetic mutation. In total, more than three thousand individuals were evaluated and studied from each family's family tree.
Demographic, surgical and histopathological data were obtained from medical records. Clinical aspects, growth, development and family history of cancer were reevaluated at semi-annual or annual returns.
Clinical signs of accelerated growth, weight gain and virilization are present in 90% of cases and 10% of cases may be asymptomatic. Clinical suspicion is confirmed by hormonal levels and imaging tests. Elevated levels of corticosteroids in the blood or urine and a mass in the adrenal region usually suggest a preoperative diagnosis of an adrenocortical tumor.
According to a pediatric oncologist, surgery with complete resection of the tumor is the most effective treatment for localized disease. For metastatic disease or recurrence, the prognosis is poor, but complete removal of the tumor associated with chemotherapy increases the chance of cure.
“The pediatrician has three relevant roles: early identification of the tumor, monitoring these children after treatment and surveillance of the patient and asymptomatic individuals carrying the mutation at risk of developing cancer with the appropriate referral to reference centers, if necessary”, recommends Maria José.
Since 2003, study patients have followed the same clinical and laboratory follow-up protocol to diagnose the mutation among family members, early detection of recurrence, detection and treatment of therapy sequelae, and assessment of the development of cancer in family members.
The research showed that a Transmission of the mutation follows a genetic pattern: 50% of the children of a carrier father or mother will inherit the mutation. The research showed that the cumulative risk for those carrying the mutation up to 45 years of age is 21% for breast, gastrointestinal, laryngeal and central nervous system cancers and this rate increases with age.
"Families that had hereditary transmission of the gene TP53 p.Arg337His have a 5,7 times greater risk of developing some type of cancer. Individuals will develop the disease later in the reproductive phase and may transmit the mutation to their descendants. We can then say that there will be an increase in cancer in Brazil, especially in the Campinas region”, explains Maria José.
The researcher warns that the identification of the mutation has a psychological impact on the family with ethical repercussions to be considered when conducting communication, recommending testing for other family members and providing guidance for monitoring those identified as positive.
“Ideally, guidance should be offered by the patient's own doctor and team, advised by a geneticist, respecting the ethical principles for decision-making, privacy protection and discussion of the risks and benefits regarding the application of the test and cancer prevention measures in the family”, recommends Maria José.
