# Diagnostic and prognostic utility of insulinoma-associated protein 1, insulin gene enhancer protein 1, and secretagogin in pheochromocytoma

## TL;DR

This study examines the usefulness of specific proteins in diagnosing and predicting outcomes for pheochromocytoma, a type of adrenal gland tumor.

## Contribution

The study evaluates the diagnostic and prognostic value of second-generation neuroendocrine markers in pheochromocytoma for the first time.

## Key findings

- Insulin gene enhancer protein 1 showed the highest staining scores among the tested markers.
- Insulinoma-associated protein 1 correlated positively with tumor proliferation index (Ki67).
- Secretagogin had low positivity, indicating limited utility as a marker in this context.

## Abstract

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.

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 μm-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.

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, only four (13.3%) patients were in the well-differentiated-type (0–2 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.

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.