Kristin Astrid Øystese1,2,3, Olivera Casar-Borota4,5,6, Kjersti Ringvoll Normann2,3, Manuela Zucknick7, Jens Petter Berg2,8, Jens Bollerslev1,2. 1. Department of Endocrinology, Section of Specialized Endocrinology, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway. 2. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway. 3. Research Institute for Internal Medicine, OUS Rikshospitalet, 0424 Oslo, Norway. 4. Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, 751 85 Uppsala, Sweden. 5. Department of Clinical Pathology and Cytology, Uppsala University Hospital, Rudbeck Laboratory, 751 85 Uppsala, Sweden. 6. Department of Pathology, Oslo University Hospital, 0372 Oslo, Norway. 7. Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway. 8. Department of Medical Biochemistry, Oslo University Hospital, 0424 Oslo, Norway.
Abstract
Context: Nonfunctioning pituitary adenomas (NFPAs) are fairly common and require a multidisciplinary approach. Reliable markers of a clinically aggressive course are lacking. Medical treatment is not available, and transsphenoidal surgery is the preferred primary treatment. Objective: We aimed to characterize the somatostatin, estrogen, and progesterone receptor distribution for NFPAs and compare it with factors of tumor aggressiveness. Design: Tumor samples for immunohistochemistry (n = 145) and quantitative reverse transcription polymerase chain reaction (n = 106) analyses of somatostatin receptor (SSTR) 1, SSTR2, SSTR3, SSTR5, estrogen receptor α (ERα), and progesterone receptor (PR) were measured by immunoreactive score (IRS) and messenger RNA relative quantity and retrospectively compared with variables of aggressiveness. Setting: All patients were operated at the same tertiary referral center. Participants: A total of 164 patients with NFPA and tumor tissue from the primary operation were included. Results: SSTR3 was expressed abundantly by immunohistochemistry in all NFPAs. The IRS of ERα correlated with that of SSTR2 in male patients only (males, P < 0.001; females, P = 0.8). Low ERα level was linked to a higher reintervention rate (P = 0.001) and earlier reintervention (P = 0.004) in male patients only (females, P = 0.95 and P = 0.65, respectively). Absence of ERα together with age provided a good prediction model for reintervention in male patients with gonadotroph adenomas. Conclusions: SSTR3 is expressed abundantly in NFPAs and is therefore a possible target for medical treatment. Absence of ERα together with young age may predict tumor recurrence in groups of NFPAs. Further validation in systematic prospective studies is needed.
Context: Nonfunctioning pituitary adenomas (NFPAs) are fairly common and require a multidisciplinary approach. Reliable markers of a clinically aggressive course are lacking. Medical treatment is not available, and transsphenoidal surgery is the preferred primary treatment. Objective: We aimed to characterize the somatostatin, estrogen, and progesterone receptor distribution for NFPAs and compare it with factors of tumor aggressiveness. Design: Tumor samples for immunohistochemistry (n = 145) and quantitative reverse transcription polymerase chain reaction (n = 106) analyses of somatostatin receptor (SSTR) 1, SSTR2, SSTR3, SSTR5, estrogen receptor α (ERα), and progesterone receptor (PR) were measured by immunoreactive score (IRS) and messenger RNA relative quantity and retrospectively compared with variables of aggressiveness. Setting: All patients were operated at the same tertiary referral center. Participants: A total of 164 patients with NFPA and tumor tissue from the primary operation were included. Results:SSTR3 was expressed abundantly by immunohistochemistry in all NFPAs. The IRS of ERα correlated with that of SSTR2 in male patients only (males, P < 0.001; females, P = 0.8). Low ERα level was linked to a higher reintervention rate (P = 0.001) and earlier reintervention (P = 0.004) in male patients only (females, P = 0.95 and P = 0.65, respectively). Absence of ERα together with age provided a good prediction model for reintervention in male patients with gonadotroph adenomas. Conclusions: SSTR3 is expressed abundantly in NFPAs and is therefore a possible target for medical treatment. Absence of ERα together with young age may predict tumor recurrence in groups of NFPAs. Further validation in systematic prospective studies is needed.
Authors: C Di Somma; E Scarano; G de Alteriis; L Barrea; E Riccio; R Arianna; S Savastano; A Colao Journal: J Endocrinol Invest Date: 2020-09-07 Impact factor: 4.256