Predicting Response to Medical Treatment in Acromegaly via Granulation Pattern, Expression of Somatostatin Receptors Type 2 and 5 and E-Cadherin.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Receptors, Somatostatin*/metabolism ; Acromegaly*/drug therapy ; Acromegaly*/metabolism ; Cadherins*/metabolism; Humans ; Female ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Somatostatin/analogs & derivatives ; Somatostatin/therapeutic use ; Somatostatin/metabolism ; Aged ; Insulin-Like Growth Factor I/metabolism ; Treatment Outcome ; Human Growth Hormone/analogs & derivatives

Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry (IHC), we assessed the expression of the somatostatin receptor subtypes SSTR2 and SSTR5, E-Cadherin, and cytokeratin granulation pattern (sparsely or densely). Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Patients resistant to fgSRL (n = 12) exhibited lower SSTR2 and E-Cadherin expressions. Sparsely granulated tumors were more frequent in the non-responder group. SSTR2 ( p = 0.024, r = 0.49) and E-Cadherin ( p = 0.009, r = 0.64) positively correlated with the Insulin-like Growth Factor 1 (IGF-1) decrease after fgSRL, while SSTR5 ( p = 0.107, r = -0.37) showed a trend towards negative correlation. SSTR5 positivity seemed to be associated with Pasireotide response, albeit the number of treated patients was too low (n = 4). No IHC markers correlated with Pegvisomant response. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2.

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25/26.05.2022 SC KOMTUR PHARMACEUTICALS SRL

Keywords: acromegaly; biomarkers; immunohistochemistry; somatostatin receptor ligands; treatment response

0 (Receptors, Somatostatin)
0 (Cadherins)
8X85ZJG6XJ (somatostatin receptor 5)
0 (SSTR2 protein, human)
51110-01-1 (Somatostatin)
67763-96-6 (Insulin-Like Growth Factor I)
N824AOU5XV (pegvisomant)
98H1T17066 (pasireotide)
D73QL0OMU2 (somatostatin receptor 2)
12629-01-5 (Human Growth Hormone)

Date Created: 20240829 Date Completed: 20240829 Latest Revision: 20240903

20240903

PMC11354630

10.3390/ijms25168663

39201352