{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:48:11Z","timestamp":1785422891741,"version":"3.56.0"},"reference-count":28,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-15-00269"],"award-info":[{"award-number":["24-15-00269"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["24-15-00269"],"award-info":[{"award-number":["24-15-00269"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Background: Primary hyperparathyroidism (PHPT) is usually caused by parathyroid tumors, resulting in hypercalcemia due to excessive PTH secretion. While disease severity correlates with calcium blood levels, the molecular mechanisms driving clinical variability remain unclear. The role of the calcium-sensing receptor (CaSR), the vitamin D receptor (VDR) and parathyroid cells mitochondrial activity in the pathogenesis of hyperparathyroidism is of particular interest. Methods: This retrospective study included 96 patients with PHPT who underwent parathyroidectomy. Patients were stratified into four groups according to the baseline albumin-corrected serum calcium assessed at diagnosis, before the initiation of calcimimetic therapy (\u22642.8; 2.8 &lt; Ca corr. \u2264 3.0; 3.0 \u2264 Ca corr. &lt; 3.5; Ca corr. \u2265 3.5 mmol\/L). Immunohistochemical expression (IHC) was estimated using CaSR, VDR, and antimitochondrial antibodies (AMA). Antibodies to VDR (GeneTex), CaSR (5C10, GeneTex), AMA (113-1, BioGenex) were used. Kidney tissue served as a positive control for CaSR and VDR antibodies, and liver tissue was used as a positive control for AMA. Statistical analysis was performed using the Statistica v. 13.3 software package (TIBCO Software Inc., Palo Alto, CA, USA; 2017). Results: Strong CaSR expression was observed in 95.8% of tumors, whereas VDR expression was reduced in 46.9%. AMA staining was heterogeneous, with high reactivity in oncocytic cells. No significant differences in CaSR, VDR, or AMA expression were found across groups with different hypercalcemia severity. No significant associations were identified between IHC marker expression and parameters of calcium-phosphorus metabolism, as well as cinacalcet treatment response. Conclusions: Despite their established roles in parathyroid regulation, CaSR and VDR expression did not correlate with hypercalcemia severity in PHPT. These findings suggest that alternative molecular mechanisms, rather than receptor expression levels, contribute to clinical heterogeneity. Further research is required.<\/jats:p>","DOI":"10.3390\/cimb48080766","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunohistochemical Expression of CaSR, VDR, and AMA in Parathyroid Tumors in Relation to Hypercalcemia Severity in Primary Hyperparathyroidism"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6667-062X","authenticated-orcid":false,"given":"Anna K.","family":"Eremkina","sequence":"first","affiliation":[{"name":"Department of Parathyroid Pathology and Mineral Disorders, Endocrinology Research Centre, Dmitry Ulyanov St., 11, 117036 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariya A.","family":"Pastuhova","sequence":"additional","affiliation":[{"name":"Laboratory of Pathomorphology, Endocrinology Research Centre, Dmitry Ulyanov St., 11, 117036 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-8522","authenticated-orcid":false,"given":"Anastasiia P.","family":"Pershina-Miliutina","sequence":"additional","affiliation":[{"name":"Digital Transformation Department, Endocrinology Research Centre, Dmitry Ulyanov St., 11, 117036 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2669-9457","authenticated-orcid":false,"given":"Anna M.","family":"Gorbacheva","sequence":"additional","affiliation":[{"name":"Department of Parathyroid Pathology and Mineral Disorders, Endocrinology Research Centre, Dmitry Ulyanov St., 11, 117036 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanum V.","family":"Bagirova","sequence":"additional","affiliation":[{"name":"Department of Parathyroid Pathology and Mineral Disorders, Endocrinology Research Centre, Dmitry Ulyanov St., 11, 117036 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-0009","authenticated-orcid":false,"given":"Liliya S.","family":"Urusova","sequence":"additional","affiliation":[{"name":"Laboratory of Pathomorphology, Endocrinology Research Centre, Dmitry Ulyanov St., 11, 117036 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya G.","family":"Mokrysheva","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre, Dmitry Ulyanov St., 11, 117036 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R56","DOI":"10.1530\/EC-17-0283","article-title":"Diagnosis, management, histology and genetics of sporadic primary hyperparathyroidism: Old knowledge with new tricks","volume":"7","author":"Mizamtsidi","year":"2018","journal-title":"Endocr. 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