title: Adrenocortical carcinoma is a lynch syndrome-associated cancer.
abstract: OBJECTIVE
  Adrenocortical carcinoma (ACC) is an endocrine malignancy with a poor prognosis. The association of adult-onset ACC with inherited cancer predisposition syndromes is poorly understood. Our study sought to define the prevalence of Lynch syndrome (LS) among patients with ACC.
  
  
  METHODS
  One hundred fourteen patients with ACC were evaluated in a specialized endocrine oncology clinic and were prospectively offered genetic counseling and clinical genetics risk assessment (group 1). In addition, families with known mismatch repair (MMR) gene mutations that were recorded in the University of Michigan Cancer Genetics Registry were retrospectively reviewed for the presence of ACC (group 2). ACC tumors from patients with LS were tested for microsatellite instability and immunohistochemistry (IHC) to evaluate for MMR deficiency.
  
  
  RESULTS
  Ninety-four (82.5%) of 114 patients with ACC underwent genetic counseling (group 1). Three individuals (3.2%) had family histories suggestive of LS. All three families were found to have MMR gene mutations. Retrospective review of an additional 135 MMR gene-positive probands identified two with ACC (group 2). Four ACC tumors were available (group 1, 3; group 2, 1). All four tumors were microsatellite stable; three had IHC staining patterns consistent with germline mutation status.
  
  
  CONCLUSIONS
  The prevalence of LS among patients with ACC is 3.2%, which is comparable to the prevalence of LS in colorectal and endometrial cancer. Patients with ACC and a personal or family history of LS tumors should be strongly considered for genetic risk assessment. IHC screening of all ACC tumors may be an effective strategy for identifying patients with LS.
authors.affiliation: University of Michigan, Ann Arbor, MI, USA. vraymond@umich.edu
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Raymond
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Everett
authors.forename: Larissa V
authors.initials: LV
authors.lastname: Furtado
authors.forename: Shanna L
authors.initials: SL
authors.lastname: Gustafson
authors.forename: Chelsy R
authors.initials: CR
authors.lastname: Jungbluth
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hammer
authors.forename: Elena M
authors.initials: EM
authors.lastname: Stoffel
authors.forename: Joel K
authors.initials: JK
authors.lastname: Greenson
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Giordano
authors.forename: Tobias
authors.initials: T
authors.lastname: Else
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult