Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH-producing adenomas
Por:
Gil, J, Marques-Pamies, M, Jorda, M, Fajardo-Montanana, C, Garcia-Martinez, A, Sampedro, M, Serra, G, Salinas, I, Blanco, A, Valassi, E, Sesmilo, G, Carrato, C, Camara, R, Lamas, C, Casano-Sancho, P, Alvarez, CV, Bernabeu, I, Webb, SM, Pico, A, Marazuela, M, Puig-Domingo, M, Santos, A, Vida-Pardo, J.I.
Publicada:
1 may 2021
Ahead of Print:
1 mar 2021
Resumen:
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.
Filiaciones:
Gil, J:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Cami Escoles S-N, Badalona 08916, Barcelona, Spain
Marques-Pamies, M:
Germans Trias & Pujol Univ Hosp, Dept Endocrinol & Nutr, Badalona, Spain
Jorda, M:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Cami Escoles S-N, Badalona 08916, Barcelona, Spain
Fajardo-Montanana, C:
Hosp Univ La Ribera, Dept Endocrinol, Alzira, Spain
Garcia-Martinez, A:
Hosp Gen Univ Alicante, Inst Hlth & Biomed Res ISABIAL, Alicante, Spain
Inst Hlth Carlos III ISCIII, Biomed Res Networking Ctr Rare Dis CIBERER, Madrid, Spain
Sampedro, M:
Inst Hlth Carlos III ISCIII, Biomed Res Networking Ctr Rare Dis CIBERER, Madrid, Spain
Univ Autonoma Madrid, Inst Princesa, Hosp Princesa, Dept Endocrinol & Nutr, Madrid, Spain
Serra, G:
Son Espases Univ Hosp, Dept Endocrinol & Nutr, Palma de Mallorca, Spain
Salinas, I:
Germans Trias & Pujol Univ Hosp, Dept Endocrinol & Nutr, Badalona, Spain
Blanco, A:
Germans Trias & Pujol Univ Hosp, Dept Neurosurg, Badalona, Spain
Valassi, E:
Univ Autonoma Barcelona, Hosp Sant Pau, Dept Endocrinol Med,IIB SPau, Res Ctr Pituitary Dis,CIBERER,ISCIII,U747, Barcelona, Spain
Sesmilo, G:
Hosp Univ Dexeus, Dept Endocrinol & Nutr, Barcelona, Spain
Carrato, C:
Germans Trias & Pujol Univ Hosp, Dept Pathol, Badalona, Spain
Camara, R:
Hosp Univ & Politecn La Fe, Dept Endocrinol & Nutr, Valencia, Spain
Lamas, C:
Hosp Gen Univ Albacete, Dept Endocrinol & Nutr, Albacete, Spain
Casano-Sancho, P:
Inst Hlth Carlos III ISCIII, Biomed Res Networking Ctr Rare Dis CIBERER, Madrid, Spain
Univ Barcelona, Hosp Sant Joan Deu, Inst Recerca Pediat, Esplugues, Spain
Alvarez, CV:
Univ Santiago De Compostela USC, Inst Invest Sanitaria IDIS, Ctr Invest Med Mol & Enfermedades Cron CIMUS, Neoplasia & Endocrine Differentiat P0L5, Santiago De Compostela, Spain
Bernabeu, I:
Complejo Hosp Univ Santiago De Compostela CHUS SE, Dept Endocrinol & Nutr, Santiago De Compostela, Spain
Webb, SM:
Univ Autonoma Barcelona, Hosp Sant Pau, Dept Endocrinol Med,IIB SPau, Res Ctr Pituitary Dis,CIBERER,ISCIII,U747, Barcelona, Spain
Pico, A:
Inst Hlth Carlos III ISCIII, Biomed Res Networking Ctr Rare Dis CIBERER, Madrid, Spain
Autonomous Univ Barcelona UAB, Dept Med, Barcelona, Spain
Marazuela, M:
Inst Hlth Carlos III ISCIII, Biomed Res Networking Ctr Rare Dis CIBERER, Madrid, Spain
Puig-Domingo, M:
Germans Trias & Pujol Res Inst IGTP, Endocrine Res Unit, Cami Escoles S-N, Badalona 08916, Barcelona, Spain
Germans Trias & Pujol Univ Hosp, Dept Endocrinol & Nutr, Badalona, Spain
Inst Hlth Carlos III ISCIII, Biomed Res Networking Ctr Rare Dis CIBERER, Madrid, Spain
Autonomous Univ Barcelona UAB, Dept Med, Barcelona, Spain
Santos, A:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Vida-Pardo, J.I.:
Hospital Lucus Augusti, Lugo, Spain
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