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Published in: Pituitary 4/2018

01-08-2018

Germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene and somatostatin receptor 1–5 and AIP immunostaining in patients with sporadic acromegaly with poor versus good response to somatostatin analogues

Authors: Hande Mefkure Ozkaya, Nil Comunoglu, Muge Sayitoglu, Fatma Ela Keskin, Sinem Firtina, Khusan Khodzhaev, Tugce Apaydin, Nurperi Gazioglu, Necmettin Tanriover, Buge Oz, Pinar Kadioglu

Published in: Pituitary | Issue 4/2018

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Abstract

Objective

To determine aryl hydrocarbon interacting protein (AIP) gene variations and AIP and somatostatin receptor (SSTR) 1–5 immunostaining in patients with apparently sporadic acromegaly with poor versus good response to somatostatin analogues (SRLs).

Methods

A total of 94 patients (66 with poor and 28 with good response to SRLs) were screened for the AIP gene variations using Sanger sequencing. Immunostaining was performed in 60 tumors.

Results

Several variations, albeit some with undetermined significance, were detected, especially in poor responder patients. The prevalence of AIP mutation was 2.1% in the whole group and 1.5% in patients with poor response to SRLs. AIP, SSTR2A, and SSTR2B immunostainings were decreased in patients with poor response (p < 0.05 for all), and other SSTRs did not differ between the groups (p > 0.05 for all). Patients with low AIP had decreased levels of SSTR2A and SSTR3 (p < 0.05 for all). AIP and SSTR2A immunostainings were positively correlated to the treatment response and age at diagnosis was negatively correlated (p < 0.05 for all). In poor responder patients with high SSTR2A immunostaining, SSTR2B immunostaining and preoperative tumor size were positively and negatively correlated, respectively, to SRL response (p < 0.05 for all).

Conclusions

Lack of response to SRLs does not necessarily increase the risk of harboring AIP mutations. The finding of decreased AIP, SSTR2A, and SSTR2B immunostaining in patients with poor response to SRLs and decreased SSTR2A and SSTR3 level in those with low AIP immunostaining suggests a possible interaction between AIP and some SSTR subtypes that might alter SRL sensitivity.
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Metadata
Title
Germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene and somatostatin receptor 1–5 and AIP immunostaining in patients with sporadic acromegaly with poor versus good response to somatostatin analogues
Authors
Hande Mefkure Ozkaya
Nil Comunoglu
Muge Sayitoglu
Fatma Ela Keskin
Sinem Firtina
Khusan Khodzhaev
Tugce Apaydin
Nurperi Gazioglu
Necmettin Tanriover
Buge Oz
Pinar Kadioglu
Publication date
01-08-2018
Publisher
Springer US
Published in
Pituitary / Issue 4/2018
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-018-0876-4

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