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Differences in somatostatin receptor subtype expression in patients with acromegaly: new directions for targeted
Lena Rass1, Amir-Hossein Rahvar2, Jakob Matschke3
1Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
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.
Insights
This study analyzed somatostatin receptor (SSTR) expression in pituitary adenomas. While immunohistochemistry is effective for SSTR2a and SSTR5 detection, no significant correlation was found with tumor characteristics or treatment response.
Area of Science:
- Endocrinology
- Oncology
- Pathology
Background:
- Somatotrophic pituitary adenomas overproduce growth hormone.
- Somatostatin analogs (SAs) are used to treat these tumors.
- Understanding somatostatin receptor (SSTR) expression is crucial for SA therapy efficacy.
Purpose of the Study:
- To analyze SSTR2a and SSTR5 expression in pituitary adenomas using immunohistochemistry (IHC).
- To correlate SSTR expression with tumor size, clinical, biochemical, and histological features.
- To assess the relationship between SSTR expression and response to SA therapy.
Main Methods:
- Immunohistochemistry (IHC) was performed on 43 surgically resected pituitary adenomas.
- Monoclonal antibodies were used to detect SSTR2a and SSTR5 expression.
- Expression levels were categorized as low, moderate, or high.
- Clinical, biochemical (hGH, IGF-1), radiological, and histological data were evaluated.
Main Results:
- SSTR2a was detected in all samples; SSTR5 was detected in 39 samples.
- High SSTR2a expression was observed in 36 samples; high SSTR5 expression in 26 samples.
- No significant correlation was found between SSTR expression and tumor size, clinical, biochemical, or histological parameters.
- Smaller adenomas showed lower baseline growth hormone (GH) levels (p=0.015).
Conclusions:
- IHC is a suitable method for determining SSTR2a and SSTR5 protein expression.
- Conclusions regarding receptor subtypes cannot be solely based on analyzed parameters.
- Further research is needed to fully understand the clinical implications of SSTR expression in pituitary adenomas.
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