Abstract
PurposeTo analyze the expression of somatostatin receptor (SSTR)2a and 5 by immunohistochemistry (IHC) in surgically resected somatotrophic pituitary adenomas and to associate expression rates with tumor size and clinical, biochemical, and histological parameters and response to somatostatin analog (SA) therapy.MethodsForty-three microsurgically treated patients with histopathologically proven growth hormone (GH)–producing pituitary adenoma were included (WHO 2017). SSTR subtype expression was analyzed in adenoma tissues using monoclonal antibodies (Abcam, SSTR2a-UMB1, SSTR5-UMB4). Expression rates were classified as low (≤ 20% staining positivity), moderate (21–50%), and high (> 50%). Furthermore, biochemical parameters such as human growth hormone (hGH) and insulin-like growth factor-1 (IGF-1) levels were measured and clinical, biochemical, radiological, and histological data were evaluated.ResultsOf the 43 patients included in this study, 28 were female and 15 were male. The median age was 52 years (range 17–72 years). The median tumor size was 1.2 cm (range: 0.13–3.93 cm). All resected tumors showed positivity for somatotrophic hormone (STH). In all tissue samples, SSTR2a signal expression was detectable in immunohistochemistry, while only 39 samples were positive for SSTR5. Thirty-six samples had a high expression of SSTR2a, while three had a moderate and four a low SSTR2a signal. In comparison, SSTR5 signal was high in 26 out of 43 samples, while seven adenomas showed a moderate and six cases a low expression rate of SSTR5. The median IGF-1 was 714.2 µg/l and the median GH 19.6 mU/l (= 6.53 µg/l). The present study indicates that there is no significant relationship between the expression rates of receptor subtypes and the parameters we analyzed. However, our study revealed that smaller adenomas have a lower baseline GH level (p = 0.015),ConclusionIHC with monoclonal antibodies appears to be a suitable method to determine the expression rates of SSTR2a and 5 at protein levels, as it is not possible to draw conclusions regarding receptor subtypes solely on the basis of the parameters analyzed.
Highlights
Is a rare endocrinological disease caused by an excess of growth hormone (GH), known as somatotropin
Looking at the somatostatin receptor distribution among densely granulated (DG) and sparsely granulated (SG) tumors, our analysis revealed that the majority of DG (91.67%, 22/24) had high expression of SSTR2a, while it was slightly less in SG (73.68%, 14/19), which has been confirmed in several studies [25, 28, 29, 39, 49]
To the majority of previous reports, our findings demonstrated that SG compared to DG more often occurred at younger age and had a larger volume at the time of diagnosis, which may be partly explained by the increased Ki67 in SG and young patients, as this was seen in about half of the cases in our cohort [25, 29, 41, 46, 48, 51, 52]
Summary
Is a rare endocrinological disease caused by an excess of growth hormone (GH), known as somatotropin. The therapy of pituitary adenomas is currently based on three different strategies, including transsphenoidal surgery (TSS), pharmacotherapy, and radiotherapy. TSS is the first-line treatment for patients with pituitary adenoma and acromegaly [5]. In all patients not suitable for surgery or in whom the tumor tissue could not be completely removed, first-generation long-acting somatostatin analogs (LA-SSAs octreotide and lanreotide) are regarded as the primary choice of pharmacotherapy [5]. Current meta-analyses demonstrate that the response rate to SSAs is about 56% for GH and 55% for insulin-like growth factor-1 (IGF-1) normalization. In treatment-naïve patients, GH normalization can be achieved in about 40% [10, 11]
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