Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly
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 patholo...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2022/8660470 |
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| author | George Kontogeorgos Vyron Markussis Eleni Thodou Efi Kyrodimou Theodossia Choreftaki Panagiotis Nomikos Kostas I. Lampropoulos Stylianos Tsagarakis |
| author_facet | George Kontogeorgos Vyron Markussis Eleni Thodou Efi Kyrodimou Theodossia Choreftaki Panagiotis Nomikos Kostas I. Lampropoulos Stylianos Tsagarakis |
| author_sort | George Kontogeorgos |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ef7d37349b254c6caebd78f250e7d9ac |
| institution | Kabale University |
| issn | 1687-8345 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-ef7d37349b254c6caebd78f250e7d9ac2025-02-03T06:12:59ZengWileyInternational Journal of Endocrinology1687-83452022-01-01202210.1155/2022/8660470Association of Pathology Markers with Somatostatin Analogue Responsiveness in AcromegalyGeorge Kontogeorgos0Vyron Markussis1Eleni Thodou2Efi Kyrodimou3Theodossia Choreftaki4Panagiotis Nomikos5Kostas I. Lampropoulos6Stylianos Tsagarakis7First Propaedeutic Department of Internal MedicineIndependent ResearchDepartment of PathologyDepartment of Pathology and Pituitary Tumor Reference CenterDepartment of Pathology and Pituitary Tumor Reference CenterDepartment of NeurosurgeryDepartment of Gamma Knife RadiosurgeryDepartment of EndocrinologyBackground. 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.http://dx.doi.org/10.1155/2022/8660470 |
| spellingShingle | George Kontogeorgos Vyron Markussis Eleni Thodou Efi Kyrodimou Theodossia Choreftaki Panagiotis Nomikos Kostas I. Lampropoulos Stylianos Tsagarakis Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly International Journal of Endocrinology |
| title | Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly |
| title_full | Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly |
| title_fullStr | Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly |
| title_full_unstemmed | Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly |
| title_short | Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly |
| title_sort | association of pathology markers with somatostatin analogue responsiveness in acromegaly |
| url | http://dx.doi.org/10.1155/2022/8660470 |
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