Immunohistochemical study of somatostatin and dopamine receptors (SSTR2, SSTR5, DR2) in pituitary adenomas to justify targeted therapy

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Abstract

Introduction. Adenomas are the most common disease affecting the pituitary gland. Most of these tumors can be successfully treated. The main method is transsphenoidal resection. The exception is prolactinomas, which are treated with dopamine agonists.

Objective. Analysis of DR2, SSTR2, SSTR5 expression in various adenomas and normal adenohypophysis to justify targeted therapy.

Material and methods. Histological and immunohistochemical examination of surgical material from 42 pituitary adenomas and 6 pituitary glands without pathology (autopsy) with SSTR2, SSTR5, DR2 markers, ACTH, PRL, GH, FSH, LH, TSH hormones. Of these, 22 prolactinomas of patients undergoing preoperative treatment with cabergoline, 10 corticotropin, 10 zero-cell adenomas; 6 pituitary glands without pathology (control group). Receptor expression was assessed in points from 1 to 4.

Results. DR2 were expressed in 39 of 42 adenomas and in all 6 normal adenohypophysis; SSTR2 – in 12 adenomas and all normal adenohypophysis, SSTR5 – in 29 and 6, respectively. Statistical analysis did not reveal a significant difference in DR2 expression in different types of adenomas; in prolactinomas and normal adenohypophysis; in the level of SSTR2 and SSTR5 expression in corticotropinomas and normal adenohypophysis; SSTR5 and DR2 in a group with 19 prolactinomas, 2 mammosomatropinomas, 1 plurihormonal adenoma (the last 3 were considered by clinicians as prolactinomas).

Conclusion. There is no significant difference in DR2 expression in patients with prolactinomas, zero-cell adenomas, and corticotropinomas, which raises questions about the feasibility of dopamine agonist therapy only in patients with hyperprolactinemia.

There is no significant difference in DR2 and SSTR5 expression in prolactinomas, which indicates the possibility of alternative therapy with somatostatin receptor analogs.

The pronounced expression of DR2, SSTR2, and SSTR5 not only in pituitary adenomas but also in the normal adenohypophysis raises questions about the adverse effects on unchanged adenomeres and also requires larger-scale studies.

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About the authors

Ksenia Alekseevna Guseva

Federal State Budgetary Institution «V.A. Almazov National Medical Research Centre» of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: ksuha.gus@yandex.ru
ORCID iD: 0009-0009-4477-9128
SPIN-code: 8344-2560

Clinical resident of the Department of Pathological Anatomy with clinic

Russian Federation, st. Akkuratova, 2, Saint-Petersburg, 197341

Artem Aleksandrovich Paltsev

Federal State Budgetary Institution «V.A. Almazov National Medical Research Centre» of the Ministry of Health of the Russian Federation

Email: Artem.paltsev@gmail.com
ORCID iD: 0000-0002-9966-2965
SPIN-code: 9944-1407

Head of the Department of Neurosurgery No. 6

Russian Federation, st. Akkuratova, 2, Saint-Petersburg, 197341

Lyubov Borisovna Mitrofanova

Federal State Budgetary Institution «V.A. Almazov National Medical Research Centre» of the Ministry of Health of the Russian Federation

Email: lubamitr@yandex.ru
ORCID iD: 0000-0003-0735-7822
SPIN-code: 9552-8248

Head of the Department of Pathological Anatomy with Clinic, Chief Researcher of the Pathomorphology Research Laboratory, Head of the Pathomorphology Service, pathologist of the highest category of the Pathoanatomical Department of the University Clinic., Executive Secretary of the Central Attestation Commission of the Ministry of Health of the Russian Federation according to the laboratory diagnostic profile, Deputy Chairman of the Dissertation Council on 21.1.028.04 on pathological anatomy 3.3.2, Doctor of Medical Sciences, Professor

Russian Federation, st. Akkuratova, 2, Saint-Petersburg, 197341

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Supplementary files

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2. Fig. 1. Histogram of SSTR2, SSTR5, and DR2 expression (in points) in different groups

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3. Fig. 2. Immunohistochemical study with antibody to DR2 (brown staining) in zero-cell adenoma of patient G., 47 years old – expression was estimated at 3 points out of 4 (а); in prolactinoma of patient K., 30 years old – expression was estimated at 4 points out of 4 (б); in adenohypophysis without pathology of patient A., 68 years old – expression was estimated at 3 points out of 4 (в); in corticotropinoma of patient Ch., 42 years old – expression was estimated at 3 points out of 4 (г); ×200

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4. Fig. 3. Immunohistochemical study with an antibody to SSTR2 (brown staining) in the corticotropinoma of patient K., 54 years old – expression was estimated at 3 points out of 4 (а); in the normal adenohypophysis of patient C., 58 years old – expression was estimated at 2 points out of 4 (б); in the zero-cell adenoma of patient G., 57 years old – expression is absent (в); in the prolactinoma of patient D., 61 years old – expression is absent (г); ×200

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5. Fig. 4. Immunohistochemical study with antibody to SSTR5 in corticotropinoma of patient L., 43 years old – expression was estimated at 3 points out of 4 (а); in normal adenohypophysis of patient A., 56 years old – expression was estimated at 3 points out of 4 (б); in zero-cell adenoma of patient A. – expression was estimated at 4 points out of 4 (в); in prolactinoma of patient K., 43 years old – expression was estimated at 4 points out of 4 (г); ×200

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6. Fig. 5. Medians of DR2 expression in groups with prolactinomas and adenohypophysis without documented pathology. Abscissa axis: Group 1 – group with prolactinomas; Group 2 – group with normal adenohypophysis. Ordinate axis: DR2 expression severity in points

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7. Fig. 6. Graph of SSTR2 and DR2 expression in the group with prolactinomas. Abscissa axis – cases studied, ordinate axis – expression severity of markers in points: 1 – expression in single cells; 2 – focal expression; 3 – no expression in single cells; 4 – diffuse expression in all cells

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8. Fig. 7. Graph of SSTR5 and DR2 expression in the group with prolactinomas. Abscissa axis – cases studied, ordinate axis – expression severity of markers in points: 1 – expression in single cells; 2 – focal expression; 3 – no expression in single cells; 4 – diffuse expression in all cells

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