{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T15:42:22Z","timestamp":1760715742227,"version":"build-2065373602"},"reference-count":23,"publisher":"FapUNIFESP (SciELO)","issue":"9","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kocaeli University Scientific Research Projects Coordination Unit","award":["2756"],"award-info":[{"award-number":["2756"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Assoc. Med. Bras."],"abstract":"<jats:p>SUMMARY  OBJECTIVE: The aim of this study was to assess the immunohistochemical expression of second-generation neuroendocrine markers such as insulin gene enhancer protein 1, insulinoma-associated protein 1, and secretagogin in pheochromocytoma and their prognostic value.  METHODS: The study included 30 operated pheochromocytoma patients. The tissue preparations were re-evaluated by two pathologists, and Pheochromocytoma of the Adrenal Gland Scaled Score score and Grading System for Adrenal Pheochromocytoma and Paraganglioma score were given. Four \u03bcm-thick paraffin block sections were stained with insulinoma-associated protein 1, insulin gene enhancer protein 1, and secretagogin antibodies to obtain staining intensity score, staining percentage, and H-score.  RESULTS: The mean age at diagnosis was 50.5 (\u00b115.9) years. The most common complaint was high blood pressure. A total of four patients (13.3%) had a nonfunctioning adenoma. The lesions were mostly localized in the right adrenal gland, and the median tumor size was 45.0 (35.0\u201354.2) mm. The median Ki67 proliferation index was 2.0% (0.9\u20133.0). According to the Pheochromocytoma of the Adrenal Gland Scaled Score score, nine (30.0%) patients showed the benign clinical behavior (score &lt;4), while according to the Grading System for Adrenal Pheochromocytoma and Paraganglioma score, only four (13.3%) patients were in the well-differentiated-type (0\u20132 points) group. insulinoma-associated protein 1 and insulin gene enhancer protein 1 were positive in 21 (70%) and 26 (86.7%) of the patients, respectively. However, secretagogin was positive only in six patients (20%). Among the second-generation neuroendocrine immunohistochemical markers, insulin gene enhancer protein 1 had the highest H-score. Correlation analysis showed a negative correlation between insulin gene enhancer protein 1 and tumor Hounsfield unit and a positive correlation between insulinoma-associated protein 1 and Ki67 proliferation index.  CONCLUSIONS: Insulinoma-associated protein 1, insulin gene enhancer protein 1, and secretagogin, which are second-generation neuroendocrine immunohistochemical markers, can be used in the differential diagnosis of pheochromocytoma. Notably, insulinoma-associated protein 1 may also have prognostic significance.<\/jats:p>","DOI":"10.1590\/1806-9282.20250504","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T15:03:52Z","timestamp":1760713432000},"source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic and prognostic utility of insulinoma-associated protein 1, insulin gene enhancer protein 1, and secretagogin in pheochromocytoma"],"prefix":"10.1590","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8428-1115","authenticated-orcid":false,"given":"Mehmet","family":"S\u00f6zen","sequence":"first","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4207-2833","authenticated-orcid":false,"given":"Gupse","family":"Turan","sequence":"additional","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7114-2565","authenticated-orcid":false,"given":"Zeynep","family":"Cant\u00fcrk","sequence":"additional","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8041-8161","authenticated-orcid":false,"given":"Berrin","family":"\u00c7etinarslan","sequence":"additional","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0646-8697","authenticated-orcid":false,"given":"Alev","family":"Selek","sequence":"additional","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8278-108X","authenticated-orcid":false,"given":"Mesude","family":"Tosun","sequence":"additional","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4892-6457","authenticated-orcid":false,"given":"Aziz Hakk\u0131","family":"Civriz","sequence":"additional","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0287-3716","authenticated-orcid":false,"given":"Burcu","family":"Sevin\u00e7","sequence":"additional","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-6106","authenticated-orcid":false,"given":"Emre","family":"Gezer","sequence":"additional","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6349-2976","authenticated-orcid":false,"given":"Damla","family":"K\u00f6ksalan","sequence":"additional","affiliation":[{"name":"Kocaeli University,  Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"530","published-online":{"date-parts":[[2025]]},"reference":[{"issue":"2","key":"ref1","doi-asserted-by":"crossref","first-page":"101346","DOI":"10.1016\/j.beem.2019.101346","article-title":"Pheochromocytoma: an approach to diagnosis","volume":"34","author":"Sbardella E","year":"2020","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s12022-018-9534-7","article-title":"Old, new, and emerging immunohistochemical markers in pheochromocytoma and paraganglioma","volume":"29","author":"Cheung VKY","year":"2018","journal-title":"Endocr Pathol"},{"issue":"4","key":"ref3","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.4103\/0973-1482.154942","article-title":"Very late recurrence of an apparently benign pheochromocytoma","volume":"11","author":"Thai E","year":"2015","journal-title":"J Cancer Res 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