Prevalence of germline TP53 mutations in a prospective series of unselected patients with adrenocortical carcinoma

J Clin Endocrinol Metab. 2013 Jan;98(1):E119-25. doi: 10.1210/jc.2012-2198. Epub 2012 Nov 21.


Purpose: Adrenocortical carcinoma (ACC) is a hallmark cancer in families with Li Fraumeni syndrome (LFS) caused by mutations in the TP53 gene. The prevalence of germline TP53 mutations in children diagnosed with ACC ranges from 50-97%. Although existing criteria advocate for TP53 testing in all patients with ACC regardless of age at diagnosis, the overall prevalence of germline mutations in patients diagnosed with ACC has not been well studied.

Patients and methods: A total of 114 patients with confirmed ACC evaluated in the University of Michigan Endocrine Oncology Clinic were prospectively offered genetic counseling and TP53 genetic testing, regardless of age at diagnosis or family history. Ninety-four of the 114 patients met with a genetic counselor (82.5%), with 53 of 94 (56.4%) completing TP53 testing; 9.6% (nine of 94) declined testing. The remainder (32 of 94; 34%) expressed interest in testing but did not pursue it for various reasons.

Results: Four of 53 patients in this prospective, unselected series were found to have a TP53 mutation (7.5%). The prevalence of mutations in those diagnosed over age 18 was 5.8% (three of 52). There were insufficient data to estimate the prevalence in those diagnosed under age 18. None of these patients met clinical diagnostic criteria for classic LFS. Three of the families met criteria for Li Fraumeni-like syndrome; one patient met no existing clinical criteria for LFS or Li Fraumeni-like syndrome. Three of the four patients with mutations were diagnosed with ACC after age 45.

Conclusions: Genetic counseling and germline testing for TP53 should be offered to all patients with ACC. Restriction on age at diagnosis or strength of the family history would fail to identify mutation carriers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adrenal Cortex Neoplasms / diagnosis
  • Adrenal Cortex Neoplasms / epidemiology
  • Adrenal Cortex Neoplasms / genetics*
  • Adrenocortical Carcinoma / diagnosis
  • Adrenocortical Carcinoma / epidemiology
  • Adrenocortical Carcinoma / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Female
  • Gene Frequency
  • Genes, p53 / genetics*
  • Genetic Counseling
  • Genetic Predisposition to Disease
  • Germ-Line Mutation* / physiology
  • Humans
  • Male
  • Middle Aged
  • Patient Selection
  • Prevalence
  • Prospective Studies
  • Young Adult