REVISTA DA ASSOCIACAO MEDICA BRASILEIRA, cilt.71, sa.9, 2025 (SCI-Expanded)
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 mu m-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 (+/- 15.9) 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 (35.0-54.2) mm. The median Ki67 proliferation index was 2.0% (0.9-3.0). According to the Pheochromocytoma of the Adrenal Gland Scaled Score score, nine (30.0%) patients showed the benign clinical behavior (score <4), while according to the Grading System for Adrenal Pheochromocytoma and Paraganglioma score, onlyfour (13.3%) patients were in the well-differentiated-type (0-2 points) group. insulinoma-associated protein 1and 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.