Hande Mefkure Ozkaya1, Nil Comunoglu2, Muge Sayitoglu3, Fatma Ela Keskin1, Sinem Firtina3, Khusan Khodzhaev3, Tugce Apaydin1, Nurperi Gazioglu4,5, Necmettin Tanriover4,5, Buge Oz3, Pinar Kadioglu6,7. 1. Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University, Cerrahpasa, 34303, Istanbul, Turkey. 2. Department of Pathology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. 3. Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. 4. Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. 5. Pituitary Center, Istanbul University, Istanbul, Turkey. 6. Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University, Cerrahpasa, 34303, Istanbul, Turkey. kadioglup@yahoo.com. 7. Pituitary Center, Istanbul University, Istanbul, Turkey. kadioglup@yahoo.com.
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.
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.
Authors: Maria A Tichomirowa; Anne Barlier; Adrian F Daly; Marie-Lise Jaffrain-Rea; Cristina Ronchi; Maria Yaneva; Jonathan D Urban; Patrick Petrossians; Atanaska Elenkova; Antoine Tabarin; Rachel Desailloud; Dominique Maiter; Thomas Schürmeyer; Renato Cozzi; Marily Theodoropoulou; Caroline Sievers; Ignacio Bernabeu; Luciana A Naves; Olivier Chabre; Carmen Fajardo Montañana; Vaclav Hana; Georges Halaby; Brigitte Delemer; José Ignacio Labarta Aizpún; Emmanuel Sonnet; Angel Ferrandez Longás; Marie-Thérèse Hagelstein; Philippe Caron; Günter K Stalla; Vincent Bours; Sabina Zacharieva; Anna Spada; Thierry Brue; Albert Beckers Journal: Eur J Endocrinol Date: 2011-07-13 Impact factor: 6.664
Authors: Ana Paula M Casarini; Raquel S Jallad; Emília M Pinto; Iberê C Soares; Suely Nonogaki; Daniel Giannella-Neto; Nina R Musolino; Venâncio A F Alves; Marcello D Bronstein Journal: Pituitary Date: 2009 Impact factor: 4.107
Authors: Medard F M van den Broek; Bernadette P M van Nesselrooij; Annemarie A Verrijn Stuart; Rachel S van Leeuwaarde; Gerlof D Valk Journal: Front Endocrinol (Lausanne) Date: 2019-12-10 Impact factor: 5.555
Authors: Nina Ionovici; Mara Carsote; Dana Cristina Terzea; Anca Mihaela Predescu; Anne Marie Rauten; Mihaela Popescu Journal: Rom J Morphol Embryol Date: 2020 Apr-Jun Impact factor: 1.033
Authors: Jiri Soukup; Helena Hornychova; Monika Manethova; Kvetoslava Michalova; Ludmila Michnova; Lenka Popovska; Veronika Skarkova; Tomas Cesak; David Netuka; Ales Ryska; Jan Cap; Václav Hána; Václav Hána; Michal Kršek; Eva Dvořáková; Michal Krčma; Ivica Lazurova; Věra Olšovská; Karel Starý; Peter Vaňuga; Filip Gabalec Journal: J Cell Mol Med Date: 2021-01-24 Impact factor: 5.310