Abstract
INTRODUCTION Non-functioning pituitary adenomas (NFPAs) are usually benign. However, a substantial proportion of pituitary adenomas show an aggressive behavior with local invasion and increased risk of regrowth or recurrence after surgery. The treatment of choice for these adenomas is transsphenoidal resection but it is not always successful. NFPAs express somastostatin receptors (SSTRs) thus providing a theoretical rationale for the pharmacological treatment with somatostatin analogues. However, a consistent method for evaluating SSTR expression needs to be implemented. AIM The aim of the study was to systematically evaluate the expression of SSTRs in NFPAs by quantitative PCR and by immunohistochemistry with reliable commercial antibodies and analyze their potential association with aggressive features. METHODS. In this retrospective descriptive study, 114 patients that underwent transsphenoidal surgery were evaluated. Clinical variables, histological subtype (including classification of agressive histological subtypes) and need for radiotherapy were collected to analyze potential associations between these variables and SSTR expression. Tumor size and cavernous sinus invasion data were obtained from magnetic resonance images. Cavernous sinus invasion was evaluated using the Knosp classification. Knosp grade 3 and 4 were defined as invasive. The expression of SSTRs (SSTR2. SSTR3 and SSTR5) was evaluated using a score system previously described [Venegas-Moreno et al. J Cell Mol Med. 2018;22(3):1640-1649]. RESULTS Quantitative PCR analysis revealed that SSTR3 was the predominant SSTR subtype detected, followed by SSTR2, SSTR5, and SSTR1. Immunohistochemistry data showed a similar expression pattern. However, The expression of the different SSTRs displayed a notable variability among NFPAs. Thus, 28,9% of NFPAs showed substantial SSTR2 expression, as indicated by high immunohistochemistry scores. Also, 12,3% of NFPAs displayed high SSTR5 expression while 86,8% of NFPAs displayed high SSTR3 levels. No significant associations between SSTR expression and sex, tumor size, invasion and surgical cure. Patients with elevated SSTR2 expression were younger but this association was not observed with SSTR3 and SSTR5. CONCLUSIONS No major association between SSTR expression and aggressive features was observed in NFPAs. A proportion of NFPAs displayed marked expression of SSTR2 and SSTR5 and thus, they might be considered potential candidates for therapy with somatostatin analogues. Sources of Research Support: Spanish Ministry of Health, ISCIII co-funded with Fondos FEDER (PI16/00175) and Novartis Oncology Spain.