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. 2022 Sep 26:2022:8660470.
doi: 10.1155/2022/8660470. eCollection 2022.

Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly

George Kontogeorgos  1   2 , Vyron Markussis  3 , Eleni Thodou  4 , Efi Kyrodimou  2 , Theodossia Choreftaki  2 , Panagiotis Nomikos  5 , Kostas I Lampropoulos  6 , Stylianos Tsagarakis  7
Affiliations

Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly

George Kontogeorgos et al. Int J Endocrinol. .

Abstract

Background: Somatotroph adenomas (SAs) exhibit a variable responsiveness to somatostatin analogue (SS-a) treatment, a process that is not well understood. We investigated established and novel histological markers as predictors of SS-a responsiveness.

Methods: We retrospectively investigated pathology samples from 36 acromegalic patients that underwent transsphenoidal surgery. Clinical, hormonal, and imaging data were available in 24/36 patients, before and after SS-a treatment. Specimens were semiquantitatively analyzed with immunocytochemistry for Ki-67, KER, SSTR-2, SSTR-5, ZAC-1, E-cadherin, and AIP.

Results: Collectively, 18 (50%) adenomas were each classified as densely/sparsely granulated somatotroph adenomas (DGSAs/SGSAs), respectively. Patients that received preoperative SS-a had lower expression of SSTR-2 compared to those that did not (2.0 (1.0, 3.0) vs. 3.0 (3.0, 3.0), p = 0.042). Compared with DGSAs, SGSAs had higher Ki-67 labeling index (LI) (1.0 (0.5, 1.0) vs. 2.0 (1.0, 3.5), p = 0.013), and a higher proportion of high MR T2 signal (1 (6%) vs. 6 (33%), p = 0.035), and tended to express less ZAC-1 (p = 0.061) and E-cadherin (p = 0.067). In linear regression corrected for baseline growth hormone (GH), ZAC-1 immunostaining was significantly associated with a decrease in GH levels after SS-a treatment (beta (95% confidence interval): -1.53 (-2.80, -0.26), p = 0.021). No markers were associated with changes in circulating insulin-like growth factor-I (IGF-I) after treatment with SS-a.

Conclusion: The novel marker ZAC-1 was associated with GH response to medical treatment with SS-a. The SGSA cases were characterized by higher Ki-67 values and MR T2 signals indicative of an inferior response to SS-a. These findings improve our understanding of the mechanisms underlying SA response to medical treatment.

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Conflict of interest statement

ST has received grants to his institution from Strongbridge, Crinetics, and Novartis and personal honoraria for lectures, advisory boards and support for meeting attendance from Recordati, Pfizer, and Ipsen. VM was a medical consultant for Ipsen when the study was conceived and carried out; during the analysis phase and the writing of this manuscript VM was no longer affiliated with Ipsen. The remaining authors have no relationships to disclose that could be construed as a conflict of interest with regard to this manuscript.

Figures

Figure 1
Figure 1
Sparsely granulated somatotroph adenoma with strong and extensive nuclear reactivity for ZAC-1, indicated with illustrative arrows (Immunohistochemistry, Hematoxyline-DAB, 40X).
See this image and copyright information in PMC

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