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


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Article Info

DATE

2021-10-21

AUTHORS

Lena Rass, Amir-Hossein Rahvar, Jakob Matschke, Wolfgang Saeger, Thomas Renné, Jens Aberle, Jörg Flitsch, Roman Rotermund

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. More... »

PAGES

79-89

References to SciGraph publications

  • 2014-08-17. Growth hormone tumor histological subtypes predict response to surgical and medical therapy in ENDOCRINE
  • 2017-01. Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control in HORMONES
  • 2008-06. Clinicopathological Features of Growth Hormone-producing Pituitary Adenomas: Difference among Various Types Defined by Cytokeratin Distribution Pattern Including a Transitional Form in ENDOCRINE PATHOLOGY
  • 2017-04-04. Treatment adherence and persistence with long-acting somatostatin analog therapy for the treatment of acromegaly: a retrospective analysis in BMC PHARMACOLOGY AND TOXICOLOGY
  • 2005-07. Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1–5 and correlation with receptor protein expression and tumor pathology in BREAST CANCER RESEARCH AND TREATMENT
  • 1999-06. Epidemiology of Acromegaly in PITUITARY
  • 2009-03-28. Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment in PITUITARY
  • 2007-09-14. Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy in MODERN PATHOLOGY
  • 2012-11-27. Growth hormone granulation pattern and somatostatin receptor subtype 2A correlate with postoperative somatostatin receptor ligand response in acromegaly: a large single center experience in PITUITARY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s42000-021-00327-w

    DOI

    http://dx.doi.org/10.1007/s42000-021-00327-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1142053534

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34674191


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    29 schema:description 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.
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    36 schema:keywords GH levels
    37 IGF-1
    38 MethodsForty-three
    39 PurposeTo
    40 Radiological
    41 ResultsOf
    42 SSTR subtype expression
    43 SSTR2A
    44 SSTR5
    45 acromegaly
    46 adenoma tissue
    47 adenomas
    48 age
    49 analogue therapy
    50 antibodies
    51 baseline GH levels
    52 basis
    53 biochemical parameters
    54 cases
    55 comparison
    56 conclusion
    57 data
    58 differences
    59 direction
    60 expression
    61 expression rate
    62 factor-1 levels
    63 growth factor-1 levels
    64 growth hormone
    65 high expression
    66 histological data
    67 histological parameters
    68 hormone
    69 human growth hormone
    70 immunohistochemistry
    71 insulin-like growth factor-1 levels
    72 levels
    73 low expression rate
    74 median IGF-1
    75 median age
    76 median tumor size
    77 method
    78 monoclonal antibodies
    79 mu/
    80 new directions
    81 parameters
    82 patients
    83 pituitary adenomas
    84 positivity
    85 present study
    86 protein levels
    87 rate
    88 receptor subtype expression
    89 receptor subtypes
    90 receptors
    91 relationship
    92 response
    93 samples
    94 signal expression
    95 signals
    96 significant relationship
    97 size
    98 small adenomas
    99 somatostatin analogue therapy
    100 somatostatin receptor subtype expression
    101 somatostatin receptors
    102 somatotrophic hormones
    103 somatotrophic pituitary adenoma
    104 study
    105 subtype expression
    106 subtypes
    107 suitable method
    108 therapy
    109 tissue
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    111 tumor size
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    114 schema:name Differences in somatostatin receptor subtype expression in patients with acromegaly: new directions for targeted therapy?
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