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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.
Ozkaya, Hande Mefkure; Comunoglu, Nil; Sayitoglu, Muge; Keskin, Fatma Ela; Firtina, Sinem; Khodzhaev, Khusan; Apaydin, Tugce; Gazioglu, Nurperi; Tanriover, Necmettin; Oz, Buge; Kadioglu, Pinar.
Afiliación
  • Ozkaya HM; Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University, Cerrahpasa, 34303, Istanbul, Turkey.
  • Comunoglu N; Department of Pathology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
  • Sayitoglu M; Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
  • Keskin FE; Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University, Cerrahpasa, 34303, Istanbul, Turkey.
  • Firtina S; Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
  • Khodzhaev K; Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
  • Apaydin T; Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University, Cerrahpasa, 34303, Istanbul, Turkey.
  • Gazioglu N; Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
  • Tanriover N; Pituitary Center, Istanbul University, Istanbul, Turkey.
  • Oz B; Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
  • Kadioglu P; Pituitary Center, Istanbul University, Istanbul, Turkey.
Pituitary ; 21(4): 335-346, 2018 Aug.
Article en En | MEDLINE | ID: mdl-29455389
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acromegalia / Somatostatina / Receptores de Somatostatina / Mutación de Línea Germinal / Péptidos y Proteínas de Señalización Intracelular Tipo de estudio: Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Pituitary Asunto de la revista: ENDOCRINOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acromegalia / Somatostatina / Receptores de Somatostatina / Mutación de Línea Germinal / Péptidos y Proteínas de Señalización Intracelular Tipo de estudio: Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Pituitary Asunto de la revista: ENDOCRINOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Estados Unidos