BERKELEY, CA (UroToday.com) - Adrenocortical tumor (ACT) is a rare tumor of the adrenal gland that manifests itself in a variety of ways. Its origins are not well understood, and it carries a generally poor prognosis.
ACT occurs in only 1 or 2 people per million and is even more uncommon in children.[1] Surgery is the single most important procedure in the successful treatment of ACT.[2] Combinations of chemotherapy drugs have been commonly used to treat patients with metastatic disease and those whose tumors cannot be completely removed by surgery.[2] However, for children whose tumors are completely removed, the role of chemotherapy has not been established.
The molecular mechanism of ACT in children is not known, but it is now well recognized that most of the genetic abnormalities in pediatric ACT patients are mutations in the TP53 gene, which may or may not be associated with a family history of cancer.[3, 4] Both adenoma and carcinoma can be associated with TP53 mutations. The exchange of experience, information, and data on rare cancers such as ACT is lacking, and outcomes for patients with these rare cancers can be improved through the establishment of an international registry. The establishment of the International Pediatric Adrenocortical Tumor Registry (IPACTR) in 1990 by the St. Jude Children's Research Hospital International Outreach Program offered a new opportunity to collect data, observe the course of the disease, understand variations in treatment and outcomes, examine factors that influence prognosis and quality of life, and study new therapies in an effort to improve patient outcomes. In the IPACTR, patients younger than 20 years with newly diagnosed or previously treated ACTs are enrolled by the patient's primary physician or parents. The registry captures clinical and laboratory features, imaging, treatment practices as determined by the primary physician, outcome data, and family history of cancer in a uniform manner, reviewed by an IPACTR physician for consistency, and entered into an electronic database. Central review of tumor origin with established testing methods is a requirement to enroll patients. Our research allows us to study genetic and molecular components implicated in the origins of ACT. To study these aspects, we have collected blood, tumors, and other biological samples from the enrolled patients. These samples are banked at St. Jude Children’s Research Hospital and are processed or shared according to established procedures and country-specific guidelines. Here at St. Jude, we developed a program that includes screening for TP53 mutations.[4,5,6,7,8] If a patient tests positive for any TP53 alteration, the parents are also tested, and any relative of the parental line with cancer is invited to be enrolled in our registry. We have also performed other molecular studies including gene expression and genome-sequencing analysis as well as established xenograft models for drug testing. We have also created a website for patients, parents, physicians, and students interested in learning more about the origins of ACT (www.stjude.org/ipactr). Our patients are enrolled by physicians or parents in more than 15 countries, including the United States, Brazil, Argentina, Chile, Greece, Japan, Spain, Honduras, England, and others. So far, we have molecular data resulting from analysis of 98 patients and 3 family members enrolled in IPACTR. These efforts will improve the availability of information for both patients and the medical community.
References:
- Michalkiewicz E, Sandrini R, Figueiredo B et al. Clinical and outcome characteristics of children with adrenocortical tumors: a report from the International Pediatric Adrenocortical Tumor Registry. Journal of Clinical Oncology 2004; 22: 838e845.
- Rodriguez-Galindo C, Figueiredo BC, et al. Biology, clinical characteristics, and management of adrenocortical tumors in children. Pediatr Blood Cancer 45(3):265-273, 2005.
- Petitjean A, Mathe E, et al. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 28(6):622-629, 2007.
- Pinto EM, Ribeiro RC, et al. TP53-Associated Pediatric Malignancies. Genes Cancer 2(4):485-490, 2011.
- West AN, Ribeiro RC, et al. Identification of a novel germ line variant hotspot mutant p53-R175L in pediatric adrenal cortical carcinoma. Cancer Res 66(10):5056-5062, 2006.
- Russell-Swetek A, West AN, et al. Identification of a novel TP53 germline mutation E285V in a rare case of paediatric adrenocortical carcinoma and choroid plexus carcinoma. J Med Genet 45(9):603-606, 2008.
- Pinto EM, Ribeiro RC, et al. Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor. Fam Cancer 10(1):141-146, 2011.
- Pinto EM, Ribeiro RC, Li J et al. An identical, complex TP53 mutation arising independently in two unrelated families with diverse cancer profiles: the complexity of interpreting cancer risk in carriers. Oncogenesis: 1-8, 2012
Written by:
Raul C. Ribeiro,a, b Emilia M. Pinto,a,c Gerard P. Zambetti,c Carlos Rodriguez-Galindod as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
aInternational Outreach Program
bOncology Department
cBiochemistry Department at St. Jude Children's Research Hospital, Memphis, TN, USA
dDana-Farber Cancer Institute/Boston Children’s Hospital, USA
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