Pheochromocytoma is a catecholamine-producing neuroendocrine tumor with unpredictable biological behavior. Neurotrophic Tropomyosin Receptor Kinase (NTRK), particularly tropomyosin-related receptor tyrosine kinase A (TrkA) encoded by NTRK1, mediates neurotrophin signaling and contributes to cellular differentiation. Although TrkA (NTRK1) expression has been observed in pheochromocytoma, its pathological significance remains unclear. In this study, we examined 31 surgically resected pheochromocytomas using immunohistochemistry for NTRK1, S100, tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), Ki-67, and succinate dehydrogenase complex iron sulfur subunit B (SDHB). The immunoreactive score was used to semiquantitatively evaluate the expression of NTRK1 and catecholamine-synthesizing enzymes, and their correlations with clinicopathological factors, including PASS and GAPP scores, were analyzed. NTRK1 immunoreactivity was detected in approximately 80% of tumors. High NTRK1 expression was significantly positively correlated with S100-positive sustentacular cells, TH, and DBH, but not with PNMT. In contrast, NTRK1 expression was inversely correlated with the Ki-67 labeling index. NTRK1 expression did not correlate with clinicopathological variables, PASS or GAPP scores, or SDHB status. These findings suggest that NTRK1 expression reflects structural and functional differentiation in pheochromocytoma, characterized by preserved sustentacular cell networks and catecholamine synthetic capacity rather than indicating malignant potential. Therefore, NTRK1 may serve as a differentiation-associated marker in pheochromocytoma, and further mechanistic and molecular investigations are warranted to elucidate its mechanistic role in chromaffin cell biology.
©The Author(s) 2026. Open Access. This article is licensed under a Creative Commons CC-BY International License.