Dataset Information

Familial isolated pituitary adenomas: from genetics to therapy.

ABSTRACT: According to autopsy and radiological data, pituitary adenomas (PAs) develop in approximately 15% to 20% of the population. The great majority of PAs arise sporadically and affect adults. Rarely they are diagnosed in children and adolescents. Approximately 5% of cases are thought to be familial. Inherited conditions associated with pituitary tumors include multiple endocrine neoplasia type 1 (MEN-1) and type 4 (MEN-4), (CNC) Carney Complex, and familial isolated PA (FIPA) syndrome. FIPA is an autosomal dominant condition, defined by the presence of two or more patients affected by PAs in the same kindred, and no other associated condition. Germline mutations of the aryl hydrocarbon receptor interacting protein gene located on chromosome 11q13 have been reported in 15%-40% of FIPA cases. In the remaining cases, genetic defect are unidentified. This article focuses on FIPA clinical, pathological, genetic features, and therapeutic management.

SUBMITTER: Guaraldi F

PROVIDER: S-EPMC5439841 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Familial isolated pituitary adenomas: from genetics to therapy.

Guaraldi Federica F Salvatori Roberto R

Clinical and translational science 20110201 1

According to autopsy and radiological data, pituitary adenomas (PAs) develop in approximately 15% to 20% of the population. The great majority of PAs arise sporadically and affect adults. Rarely they are diagnosed in children and adolescents. Approximately 5% of cases are thought to be familial. Inherited conditions associated with pituitary tumors include multiple endocrine neoplasia type 1 (MEN-1) and type 4 (MEN-4), (CNC) Carney Complex, and familial isolated PA (FIPA) syndrome. FIPA is an au ...[more]

PMID: 21348957

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Project description:Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses the current clinical and therapeutic characteristics of more than 200 FIPA families and addresses research findings among AIP mutation-bearing patients in different populations with pituitary adenomas.

Project description:Background and aimAbout a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates.MethodsWe performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas' classification as primary outcomes. Secondary outcomes included the TPS' relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis.ResultsEighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas' classification, we found that "proliferative" cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80-18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p = 0.001; OR: 5.44; CI 95%: 1.98-14.98), while an inverse relationship was found with FSH/LH expression (p = 0.014; OR = 0.27, CI 95%: 0.10-0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence.ConclusionsPD-L1 expression was associated with proliferative grades of Trouillas' classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.

Dataset Information

Familial isolated pituitary adenomas: from genetics to therapy.

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Familial isolated pituitary adenomas: from genetics to therapy.

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