ECE2018 Guided Posters Pituitary Clinical (12 abstracts)
Molecular profiling of non-functioning pituitary adenomas does not support pharmacological therapeutic options
Joan Gil 1 , Alberto Blanco 2 , Guillermo Serra 3 , Isabel Salinas 2 , Susan M Webb 4 , Cristina Hostalot 2 , Gabriel Obiols 5 , Elena Valassi 4 , Olga Roig 4 , Gemma Sesmilo 6 , Carles Villabona 7 , Mireia Jordà 1 & Manel Puig-Domingo 1
1Institut Germans Trias, Badalona, Spain; 2Hospital Germans Tries, Badalona, Spain; 3Hospital Son Espases, Palma de Mallorca, Spain; 4Hospital de Sant Pau, Barcelona, Spain; 5Hospital Vall d’Hebron, Barcelona, Spain; 6Hospital Quirón Dexeus, Barcelona, Spain; 7Hospital de Bellvitge, Hospitalet de Llobregat, Spain.
Non-functioning pituitary adenomas (NFPA) are the most common pituitary tumours. They usually come to medical attention because of a mass effect and/or hypopituitarism. Tumour shrinkage during therapy with either dopamine agonists (DA) or somatostatin analogues (SSA) has been previously reported in some cases; however, response of NFPA to medical treatment is still poor and unpredictable. Our aim was to explore the molecular mechanisms underlying this lack of efficacy through evaluation of genes involved in therapeutic response to SSA and DA. Expression of 13 genes was analyzed in 105 acromegaly samples (ACRO), 20 NFA and 14 control pituitaries (CP) from autopsies and organ donors. The genes (SSTR2, SSTR5, DRD2 long and short isoforms, AIP, CDH1, Ki67, ARRB1, GHRL, IN1-GHRL, KLK10, PLAGL1 and PEBP1) were measured by RT-qPCR using TaqMan technology and the levels were normalized by three reference genes (MRPL19, TBP and PGK1).
Results: DDR2, SSTR2 and SSTR5 showed significantly and absolute lower expression levels in NFA compared to ACRO (P< 0.01 for all comparisons) and CP (P< 0.01 for all comparisons). Moreover, SSTR5 levels were extremely low in NFPA, pointing to a potential absolute negative therapeutic response to the second generation SSA Pasireotide compared to first generation SSA. Unsupervised clustering showed that NFPA were extremely different from CP and ACRO tumours according to the expression of these markers. Tumour size in NFPA significantly correlated with AIP and IN1-GHRL (Pearson’s r=0.48 and P=0.03, Pearson’s=0.47 and P=0.04, respectively); and showed a trend to correlation with ARRB1 and PLAGL1 levels (Pearson’s r=0.42 and P=0.07, Pearson’s=−0.45 and P=0.05, respectively). Moreover, ARRB1 was significantly overexpressed in tumours that did not achieve complete remission after surgery (fold change =1.81, P=0.01). In addition, RKIP and KLK10 showed a positive correlation trend with extrasellar extension (fold change =1.39 and P=0.07, fold change =3.74 and P=0.07, respectively). These preliminary results suggest that some molecular markers may identify NFPA with a higher potential for growth and invasiveness, thus contributing to therapeutic decisions regarding reoperation or radiotherapy but do not support the use of targeted drug according to the studied molecular profiling.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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