[en] BACKGROUND: Pituitary adenomas have a high disease burden due to tumor growth/invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1 and AIP are associated with early onset of aggressive pituitary adenomas that can be resistant to medical therapy. AIMS: We performed a retrospective screening study using published risk criteria to assess the frequency of AIP and MEN1 mutations in pituitary adenoma patients in a tertiary-referral center. METHODS: Pituitary adenoma patients with pediatric/adolescent onset, macroadenomas occurring </=30 years of age, familial isolated pituitary adenoma (FIPA) kindreds, and acromegaly or prolactinoma cases that were uncontrolled by medical therapy were studied genetically. We also assessed whether immunohistochemical staining for AIP (AIP-IHC) in somatotropinomas was associated with somatostatin analogs (SSA) response. RESULTS: Fifty-five patients met the study criteria and underwent genetic screening for AIP/MEN1 mutations. No mutations were identified and large deletions/duplications were ruled out using MLPA. In a cohort of sporadic somatotropinomas, low AIP-IHC tumors were significantly larger (p=0.002) and were more frequently sparsely-granulated (p=0.046) than high AIP-IHC tumors. No significant relationship between AIP-IHC and SSA responses was seen. CONCLUSIONS: Germline mutations in AIP/MEN1 in pituitary adenoma patients are rare and the use of published risk criteria did not identify cases in a large tertiary-referral setting. In acromegaly, low AIP-IHC was related to larger tumor size and more frequent sparsely-granulated subtype but no relationship with SSA-responsiveness was seen. The genetics of aggressive, treatment-resistant and familial pituitary adenomas remain largely unexplained and screening criteria could be significantly refined.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Daly, Adrian ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Cano, David A.
Venegas, Eva
PETROSSIANS, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'endocrinologie clinique
Dios, Elena
CASTERMANS, Emilie ; Centre Hospitalier Universitaire de Liège - CHU > Unilab > Unité de laboratoire - endocrino - métabolique
Flores-Martinez, Alvaro
Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique humaine
Beckers, Albert ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Soto, Alfonso
Language :
English
Title :
AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center.
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