Related Experiment Video
Updated: Sep 20, 2026
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Increased HIF-2α and CD105 (endoglin) expression is associated with poor differentiation in pheochromocytomas and
1Department of Pathology, Hamidiye School of Medicine, University of Health Sciences, Konya City Hospital, Konya, Türkiye.
Objective:
Reliable biomarkers reflecting tumor biology and histopathological risk status in pheochromocytomas and paragangliomas (PPGL) remain limited. In this study, the expression of biomarkers associated with hypoxia, angiogenesis, and proliferation was evaluated, and their associations with histopathological differentiation in PPGL were investigated.
Methods:
A total of 35 tumor foci from 31 patients with PPGL who were surgically treated were retrospectively examined. Expression levels of hypoxia-inducible factor-2 alpha (HIF-2α), vascular endothelial growth factor (VEGF), CD105 (endoglin), Ki-67, and succinate dehydrogenase subunit B (SDHB) were assessed using immunohistochemical methods. Associations between these markers and clinicopathological characteristics, Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) scores were analyzed.
Results:
HIF-2α expression, CD105 microvessel density (MVD) score, and Ki-67 proliferation index were significantly higher in poorly differentiated tumors compared with moderately/well-differentiated tumors (p<0.05 for all). In contrast, VEGF expression did not differ significantly between the groups. The GAPP score showed positive correlations with HIF-2α (r=0.48; p<0.01), CD105 (r=0.54; p<0.001), and Ki-67 (r=0.77; p<0.001). In univariate analyses, bilateral disease, HIF-2α expression, CD105 MVD score, and loss of SDHB expression were associated with higher GAPP scores. However, in multivariable regression analysis, only CD105 was independently associated with the GAPP score (β=0.04; p=0.026).
Conclusion:
Increased expression of CD105, HIF-2α, and Ki-67 was associated with poorer histopathological differentiation in PPGL. Among the biomarkers evaluated, only CD105 showed an independent association with the GAPP score, suggesting that tumor-associated neoangiogenesis may contribute to histopathological differentiation in PPGL. These findings support further investigation of CD105 as a potential biomarker for histopathological risk assessment. However, larger studies with long-term clinical outcome data are needed to establish its clinical prognostic value.
