Differences in somatostatin receptor subtype expression in patients with acromegaly: new directions for targeted therapy?

Abstract

PURPOSE:

To 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.

METHODS:

Forty-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.

RESULTS:

Of 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), CONCLUSION: IHC 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.

• Authors: Lena Rass, Amir-Hossein Rahvar, Jakob Matschke, Wolfgang Saeger, Thomas Renné, Jens Aberle, Jörg Flitsch, Roman Rotermund
• Journal: Hormones (Athens, Greece) (Hormones (Athens)) Vol. 21 Issue 1 Pg. 79-89 (Mar 2022) ISSN: 2520-8721 [Electronic] Switzerland
• PMID: 34674191 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Receptors, Somatostatin
• Somatostatin

Topics

• Acromegaly (drug therapy, surgery)
• Adenoma (drug therapy, metabolism)
• Adolescent
• Adult
• Aged
• Female
• Growth Hormone-Secreting Pituitary Adenoma (drug therapy)
• Humans
• Male
• Middle Aged
• Pituitary Neoplasms (pathology)
• Receptors, Somatostatin (metabolism)
• Somatostatin (therapeutic use)
• Young Adult