El Registro Molecular de Adenomas Hipofisarios (REMAH): una apuesta de futuro de la Endocrinología española por la medicina individualizada y la investigación traslacional

Luque, Raúl M.; Ibáñez‐Costa, Alejandro; Sánchez-Tejada, Laura; Rivero‐Cortés, Esther; Robledo, Mercedes; Madrazo‐Atutxa, Ainara; Mora, Mireia; Álvarez, Clara; Lucas-Morante, Tomás; Álvarez-Escolá, Cristina; Fajardo, Carmen; Castaño, Luís; Gaztambide, Sonia; Venegas‐Moreno, Eva; Soto‐Moreno, Alfonso; Gálvez, María A.; Salvador, Javier; Valassi, Elena; Webb, Susan M.; Picó, Antonio; Puig-Domingo, Manel; Gilabert, Montserrat; Bernabéu, Ignacio; Marazuela, Mónica; Leal‐Cerro, Alfonso; Castaño, Justo P

doi:10.1016/j.endonu.2016.03.001

Cited by 20 publications

(19 citation statements)

References 33 publications

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“…The study was performed within the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a Spanish Multicentre Clinical-Basic Project [12]. The study complies with the Declaration of Helsinki and other applicable laws and received approval from the Local Ethics Committee (CEIC Hospital General Universitario de Alicante).…”

Section: Matherial and Methodsmentioning

confidence: 99%

“…We evaluated the quality and quantity of total RNA in the Nanodrop (Thermo Scientific) and the 2100 Bioanalyzer (Agilent Technologies). The protocol of retrotranscription, selection of primers and quantitative real-time-PCR (qRT-PCR) conditions were adjusted to the material and methods published by Luque et al [12]. Specifically, gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, arginine vasopressin receptor 1b, and five types of dopamine receptors ( DR1 , DR4 , DR5 , DR2 and its isoform DR2 long ) were measured by qRT-PCR.…”

Section: Matherial and Methodsmentioning

confidence: 99%

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Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas

et al. 2017

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AimThe WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling.MethodsWithin the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard.ResultsBased on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas), we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes.ConclusionsAccording to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA.

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Section: Matherial and Methodsmentioning

confidence: 99%

Section: Matherial and Methodsmentioning

confidence: 99%

Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas

et al. 2017

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“…It has been suggested that additional biomarkers could be used to predict the biological behavior of the tumor and its response to treatment. The Molecular Registry of Pituitary Adenomas (REMAH study) is a multicenter, interdisciplinary network founded on a shared database that provides a translational approach for the personalized management of pituitary adenomas by combining clinical, pathological, and molecular information [13,36]. Preliminary results from the study have confirmed the concept that GH-secreting adenomas are heterogeneous tumors with a highly variable molecular expression of genes associated with SSAs, and further suggested that E-cadherin is the best molecular discriminator of a therapeutic response to SSAs [37].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding responses to treatment with SSAs, at six months the median IGF-1 reduction for adenomas negative for E-cadherin was 8.9% compared to 49.8% in adenomas positive for E-cadherin [18]. Currently, there are no other biomarkers which have been validated in clinical practice [13,14,18,36,37,39,40]. We therefore present a suggested algorithm for the use of biomarkers in clinical practice (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Role of Receptor Profiling for Personalized Therapy in a Patient with a Growth Hormone-Secreting Macroadenoma Resistant to First-Generation Somatostatin Analogues

Alexandraki

Papadimitriou

Mavroeidi

et al. 2019

JPM

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Background: Acromegaly is almost always caused by a pituitary adenoma and is associated with high morbidity and mortality when uncontrolled. Trans-sphenoidal removal of the adenoma is the mainstay of therapy, but fails to control the disease in a significant number of patients who require further treatment. Somatostatin analogues (SSAs) as monotherapy or in combination with growth hormone (GH)-receptor antagonists and/or dopamine agonists are used either alone or in combination following surgical failure to achieve disease control. The use of specific biomarkers may help to individualize the therapeutic plan after surgical failure and direct towards a more personalized approach. Methods: We report a 41-year-old man with acromegaly and residual disease after repeated surgery that was resistant to first-generation SSAs. Results: Biochemical and tumor control were achieved following the administration of a second-generation SSA, pasireotide, combined with pegvisomant, both at maximal doses and along with cabergoline. Histology specimens showed a sparsely-granulated GH-immunostaining pituitary adenoma with intense positivity for somatostatin receptors 2 and 5 and low levels of E-cadherin. Conclusion: Personalized medical therapy guided by currently available biomarkers, such as immunohistochemically-characterized receptor profiling or adhesion molecules, resulted in controlled insulin-like growth factor-1 (IGF-1) and GH levels and symptom alleviation following the combination of three drug-classes.

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“…The Spanish Molecular Registry of Pituitary Adenomas (REMAH) network initiative allowed us to identify the molecular subtypes of PitNETs [15][16][17]. Namely, we identified the molecular subtypes of PitNETs based on the gene expression of pituitary hormones and some receptors (POMC, CRHR1, AVPR1B, PRL, TSH, GH, FSH, and LH).…”

Section: Samplesmentioning

confidence: 99%

Increased E2F1 mRNA and miR-17-5p Expression Is Correlated to Invasiveness and Proliferation of Pituitary Neuroendocrine Tumours

et al. 2020

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miR-17-5p and E2F1 have been described as deregulated in cancer, but they have scarcely been studied in pituitary neuroendocrine tumours (PitNETs). This study evaluates the relationship of E2F1 and miR-17-5p with the invasiveness and proliferation of PitNETs. In this cross-sectional descriptive study, we evaluated the expression of E2F1, MYC, and miR-17-5p by quantitative real time PCR analysis in 60 PitNETs: 29 gonadotroph (GT), 15 functioning somatotroph (ST), and 16 corticotroph (CT) tumours, of which 8 were silent (sCT). The clinical data were collected from the Spanish Molecular Register of Pituitary Adenomas (REMAH) database. We defined invasiveness according to the Knosp classification and proliferation according to a molecular expression of Ki-67 ≥ 2.59. E2F1 was more expressed in invasive than in non-invasive tumours in the whole series (p = 0.004) and in STs (p = 0.01). In addition, it was overexpressed in the silent subtypes (GTs and sCTs; all macroadenomas) and normoexpressed in the functioning ones (fCTs and STs; some microadenomas). miR-17-5p was more expressed in proliferative than in non-proliferative tumours (p = 0.041) in the whole series but not by subtypes. Conclusions: Our study suggests that in PitNETs, E2F1 could be a good biomarker of invasiveness, and miR-17-5p of proliferation, helping the clinical management of these tumours.

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El Registro Molecular de Adenomas Hipofisarios (REMAH): una apuesta de futuro de la Endocrinología española por la medicina individualizada y la investigación traslacional

Cited by 20 publications

References 33 publications

Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas

Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas

Role of Receptor Profiling for Personalized Therapy in a Patient with a Growth Hormone-Secreting Macroadenoma Resistant to First-Generation Somatostatin Analogues

Increased E2F1 mRNA and miR-17-5p Expression Is Correlated to Invasiveness and Proliferation of Pituitary Neuroendocrine Tumours

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