Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH‐producing adenomas. (14th March 2021)

• Record Type: Journal Article
• Authors: Gil, Joan; Marques‐Pamies, Montserrat; Jordà, Mireia; Fajardo‐Montañana, Carmen; García‐Martínez, Araceli; Sampedro, Miguel; Serra, Guillermo; Salinas, Isabel; Blanco, Alberto; Valassi, Elena; Sesmilo, Gemma; Carrato, Cristina; Cámara, Rosa; Lamas, Cristina; Casano‐Sancho, Paula; Alvarez, Clara V.; Bernabéu, Ignacio; Webb, Susan M.; Picó, Antonio; Marazuela, Mónica; Puig‐Domingo, Manel
• Other Names: Adrados Magdalena investigator.; Martínez Flores Pedro investigator.; Leví Ana María Ramos investigator.; Serrano‐Somavilla Ana investigator.; Paz de Miguel Novoa María investigator.; García Villanueva Mercedes investigator.; Iglesias Pedro investigator.; Rodríguez Berrocal Víctor investigator.; Blanco Concepción investigator.; Alameda Hernando Carmen investigator.; Luis Jesús Miguel Pérez investigator.; García Centeno Rogelio investigator.; Iza Begoña investigator.; Alvarez‐Escolá Cristina investigator.; Pérez Zamarrón Álvaro investigator.; Pérez López Carlos investigator.; Alén José F investigator.; Calatayud Gutiérrez María investigator.; Paredes Sansinenea Igor investigator.; Otero Álvaro investigator.; María Recio José investigator.; Sousa Pablo investigator.; Aguilló Gutiérrez Esperanza investigator.; Bances Luciano investigator.; Calvo Gracia Fernando L investigator.; Comuñas Fernando investigator.; Crespo Iris investigator.; Ma Martel Luciana investigator.; Fernando Muñoz Pau investigator.; Resmini Eugenia investigator.; Roig Olga investigator.; Santos Alicia investigator.; Tresserras Pere investigator.; Asencio Carlos investigator.; Gras Juan‐Ramón investigator.; Maria Montserrat Juan investigator.; Obiols Gabriel investigator.; Biagetti Betina investigator.; Torres Alberto investigator.; Vidal Noemí investigator.; Guanyabens Elena investigator.; Cajas Priscilla investigator.; Cuatrecasas Guillem investigator.; Enseñat Joaquim investigator.; Mora Mireia investigator.; Hansu Felicia investigator.; Halperin Irene investigator.; Buj Raquel investigator.; Villalmanzo Núria investigator.; Cecenarro Laura investigator.; Hostalot Cristina investigator.; Riesgo Pedro investigator.; Simal‐Julian Juan Antonio investigator.; Sandoval Hernán investigator.; Lamas Cristina investigator.; Abarca Javier investigator.; Arias Mendoza Nieves investigator.; Sánchez Ortiga Ruth investigator.; Monjas Irene investigator.; Aranda Ignacio investigator.; Pedro Font Teresa investigator.; Alonso Troncoso Isabel investigator.; Fernández Catalina Pablo investigator.; Álvarez San Martín Rosa María investigator.; Villar Rocío investigator.; Ballesteros María D investigator.; Pérez Romero Sihara investigator.; Fernández Rodríguez Eva investigator.; García‐Allut Alfredo investigator.; Serramito Ramón investigator.; Prieto Alma investigator.; Cotovad Bellas Laura investigator.; Vidal Pardo José‐Ignacio investigator.;
• Is Part Of: Clinical endocrinology. Volume 94:Number 5(2021)
• Page Start: 811
• Page End: 819
• Publication Date: 2021-03-14
• Subjects: acromegaly -- Ki‐67 -- RORC -- somatostatin analogs -- somatostatin receptor ligands -- transsphenoidal surgery; Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.14339
• Languages: English
• ISSNs: 0300-0664

Abstract

Abstract: Objective: Large somatotrophic adenomas depict poor response to somatostatin receptor ligands (SRLs). Debulking has shown to enhance SRLs effect in some but not all cases and tumour volume reduction has been proposed as the main predictor of response. No biological studies have been performed so far in this matter. We aimed to identify molecular markers of response to SRLs after surgical debulking in GH‐secreting adenomas. Design: We performed a multicenter retrospective study. Patients: 24 patients bearing large GH‐producing tumours. Measurements: Clinical data and SRLs response both before and after surgical debulking were collected, and 21 molecular biomarkers of SRLs response were studied in tumour samples by gene expression. Results: From the 21 molecular markers studied, only two of them predicted enhanced SRLs response after surgery. Tumours with improved response to SRLs after surgical debulking showed lower levels of Ki‐67 ( MKI67, FC = 0.17 and P = .008) and higher levels of RAR‐related orphan receptor C ( RORC) (FC = 3.1 and P ˂ .001). When a cut‐off of no detectable expression was used for Ki‐67, the model provided a sensitivity of 100% and a specificity of 52.6% with an area under the curve of 65.8%. Using a cut‐off of 2 units of relative expression of RORC, the prediction model showed 100% of sensitivity and specificity. Conclusions: High levels of RORC and low levels of Ki‐67 identify improved SRLs response after surgical debulking in large somatotropic adenomas. To determine their expression would facilitate medical treatment decision‐making after surgery.