OR26-1 REMAH: The Spanish Molecular Registry of Pituitary Adenomas. A clinical-molecular multicenter research network to study pituitary adenomas: Initial data on the molecular profile of GH-producing adenomas

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR26-Pituitary Tumorigenesis: Advances in Mechanism & Treatment
Translational
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:15 AM
Room 130 (Moscone Center)
Raul M. Luque*1, Laura Sanchez-Tejada2, Alejandro Ibañez-Costa1, Mireia Jordá3, Esther Rivero-Cortés1, Ruth Sanchez-Ortiga2, Raquel Buj3, Ainara Madrazo-Atutxa4, María Angeles Galvez5, Miguel A Japón6, Eva Venegas4, Natividad Garcia-Hernandez4, Elena Dios4, Juan Francisco Martin-Rodriguez4, Juan García-Arnés7, Francisco J Tinahones8, Pedro Riesgo9, Manuel Polaina10, Carmen Fajardo11, Elena Valassi12, Susan M. Webb12, Ignacio Bernabeu13, Inmaculada Gavilán14, Manuel Beltrán14, Alberto Moreno15, Ignacio Martin-Schrader10, Alfonso Soto-Moreno4, Pedro Benito-López5, Manuel Puig-Domingo16, Antonio Picó2, Justo Pastor Castano1 and Alfonso Leal-Cerro4
1University of Córdoba, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Cordoba, Spain, 2Hospital Universitario de Alicante, Universidad Miguel Hernández, Alicante, Spain, 3Institut de Medicina Predictiva i Personalitzada del Càncer (IMPPC), Badalona, Spain, 4Instituto de Biomedicina de Sevilla (IBiS), Consejo Superior de Investigaciones Científicas, Endocrinology Unit of Virgen del Rocío University Hospital, University of Seville, Sevilla, Spain, 5Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain, 6Virgen del Rocio University Hospital, Sevilla, Sevilla, Spain, 7Carlos Haya Hospital, Málaga, Spain, 8Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain, 9Hospital Universitario de La Ribera, Valencia, Valencia, Spain, 10Neurosurgical Unit, Sevilla, Spain, 11Hospital Universitario La Ribera, Alzira, Spain, 12Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain, 13Hospital Clinico Universitario de Santiago (CHUS), Santiago de Compostela, Spain, 14Puerta del Mar University Hospital, Cádiz, Spain, 15Complejo Hospitalario de Jaén, Jaén, Spain, 16Universitat Autònoma de Barcelona, Germans Trias i Pujol University Hospital, Badalona, Spain
Pituitary adenomas present with a variety of clinical endocrine manifestations and the prevalence has been largely underestimated (one case per ~1000 of the general population). In order to advance in the tools for the diagnosis/management of different types of pituitary adenomas, we are developing a multicenter, multidisciplinary clinical-basic project at 6 Spanish regional nodes covering all reference centers for pituitary pathology. This unique coordinated, translational network initiative, named Spanish Molecular Registry of Pituitary Adenomas (REMAH), was developed in 2010 by the Sociedad Andaluza de Endocrinología y Nutrición, and further endorsed by the Sociedad Española de Endocrinología y Nutrición, and supported by Novartis. To minimize intercenter variability, similar protocols, methods and strategies were used in all centers to collect the clinical and pathological data and the tumor samples from patients, and to obtain the molecular phenotype of each pituitary-sample. Specifically, expression levels of 26 genes were measured by quantitative real-time-PCR, including all pituitary hormones, receptors for somatostatin, dopamine, GHRH, GnRH, CRH, vasopressin and ghrelin, two proliferation markers (Ki-67, PTTG-1) and three housekeeping genes for normalization (beta actin, HPRT and GAPDH). To date, the clinical, pathological and molecular data of 634 patients are being registered in a shared database (http://www.remahnacional.com) and the number continues growing. An initial clinical/molecular analysis has been started in a series of 83 somatotropinomas, in which we have observed that somatostatin receptor (SSTR) subtype-2 was present at the highest levels followed by SSTR5>SSTR3>SSTR1. Dopamine receptor (DR)-2 was the predominant DR subtype followed by DR5>DR4>DR1. Somatotropinomas also express significant levels of GHRH and ghrelin receptor, Ki67 and PTTG-1. Patients with macroadenomas have higher circulating levels of GH and IGF-I and express more SSTR2 and ki67 mRNA levels than microadenomas. Interestingly, we observed that the expression of ghrelin-receptor was positively correlated with circulating levels of GH and IGF-I at diagnosis. Future studies using the REMAH database will be focused on determining whether a detailed knowledge of the adenoma molecular phenotyping profile could help to predict the hormonal response to therapy in order to improve the management of patients with different types of pituitary pathologies.

Disclosure: RML: Researcher, Novartis Pharmaceuticals. LS: Researcher, Novartis Pharmaceuticals. AI: Researcher, Novartis Pharmaceuticals. MJ: Researcher, Novartis Pharmaceuticals. ER: Researcher, Novartis Pharmaceuticals. RS: Researcher, Novartis Pharmaceuticals. RB: Researcher, Novartis Pharmaceuticals. AM: Researcher, Novartis Pharmaceuticals. MAG: Clinical Researcher, Novartis Pharmaceuticals. MAJ: Clinical Researcher, Novartis Pharmaceuticals. EV: Clinical Researcher, Novartis Pharmaceuticals. NG: Clinical Researcher, Novartis Pharmaceuticals. ED: Clinical Researcher, Novartis Pharmaceuticals. JFM: Investigator, Novartis Pharmaceuticals. JG: Clinical Researcher, Novartis Pharmaceuticals. FJT: Clinical Researcher, Novartis Pharmaceuticals. PR: Clinical Researcher, Novartis Pharmaceuticals. MP: Clinical Researcher, Novartis Pharmaceuticals. CF: Clinical Researcher, Novartis Pharmaceuticals. EV: Clinical Researcher, Novartis Pharmaceuticals. SMW: Clinical Researcher, Novartis Pharmaceuticals. IB: Clinical Researcher, Novartis Pharmaceuticals. IG: Clinical Researcher, Novartis Pharmaceuticals. MB: Clinical Researcher, Novartis Pharmaceuticals. AM: Clinical Researcher, Novartis Pharmaceuticals. IM: Clinical Researcher, Novartis Pharmaceuticals. AS: Clinical Researcher, Novartis Pharmaceuticals. PB: Clinical Researcher, Novartis Pharmaceuticals. MP: Clinical Researcher, Novartis Pharmaceuticals. AP: Clinical Researcher, Novartis Pharmaceuticals. JPC: Researcher, Novartis Pharmaceuticals. AL: Clinical Researcher, Novartis Pharmaceuticals.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Novartis, Sociedad Española de Endocrinología y Nutrición, Sociedad Andaluza de Endocrinología y Nutrición, Junta de Andalucía (BIO-0139, CTS-5051, CTS-444), MICINN (BFU2010-19300)
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