Diagnostic and prognostic utility of INSM1, ISL1 and secretagogin in pheochromocytoma

Abstract Background: To assess immunohistochemical expression of the second generation neuroendocrine immunohistochemical markers such as insulin gene enhancer protein 1 (ISL1), insulinoma-associated protein 1 (INSM1) and secretagogin (SECG) in pheochromocytoma (PCC) and prognostic value. Methods: The study included 30 operated PCC patients. The tissue preparations were re-evaluated by two pathologists and PASS score and GAPP score were given. 4 µm thick paraffin block sections were stained with INSM1, ISL1 and SECG antibodies to obtain staining intensity score, staining percentage and H-score. Results: Mean age at the diagnosis was 50.5 (±15.9) years. Eight patients were asymptomatic. The most common complaint was high blood pressure. 4 patients (13.3%) had nonfunctioning adenoma. The lesions were mostly localized in the right adrenal gland and median tumor size was 45.0 (35.0-54.2) mm. Median Ki67 was 2.0 % (0.9-3.0). According to the PASS score, 9 (30.0%) patients showed in the benign clinical behavior (score <4), while according to the GAPP score, only 4 (13.3%) patients in the well differentiated type (0-2 points) group. INSM1 and ISL1 were positive in 21 (70%) and 26 (86.7%) of the patients, respectively. However, SECG was positive only in 6 patients (20%). Among the second generation neuroendocrine immunohistochemical markers, ISL1 had the highest H-score. Correlation analysis showed a negative correlation between ISL1 and tumor HU and a positive correlation between INSM1 and Ki67. Conclusion: INSM1, ISL1 and SECG, which are second generation neuroendocrine immunohistochemical markers, can be used in the differential diagnosis of pheochromocytoma. In addition, especially ISNM1 may have prognostic significance.