ArticleEndocrine connections2025
Clinical significance, prognosis, and risk model of SDHB expression loss and ERBB2 expression in pheochromocytoma and paraganglioma.
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Abstract
Objective: To investigate the clinicopathological correlation, prognostic significance, and risk model of SDHB expression loss and ERBB2 expression in pheochromocytomas and paragangliomas (PPGLs). Methods: A total of 165 patients with histologically confirmed PPGLs who underwent surgery at the Cancer Hospital were enrolled. Clinical and pathological characteristics were retrospectively analyzed. Immunohistochemistry (IHC) and next-generation sequencing (NGS) methods were employed, and data were analyzed and visualized using SPSS 25.0 and R Studio. Results: Among the 165 patients (male-to-female ratio: 0.85:1; age range: 14-82 years), there were 117 cases of pheochromocytomas and 48 cases of paragangliomas. SDHB expression loss was detected in 29 patients, and SDHB expression retention was observed in 136 patients. ERBB2 overexpression was found in 47 patients and absent in 118 patients. A statistically significant correlation was observed between SDHB expression loss and ERBB2 expression (P < 0.001, R = 0.45). Survival analysis revealed significant differences in progression-free survival (P < 0.001) and overall survival (P < 0.001) between SDHB expression loss and SDHB expression retention PPGLs, as well as between ERBB2-overexpressing and low/non-expressing groups (PFS: P < 0.001; OS: P = 0.01). Univariate and multivariate COX regression analyses showed that SDHB expression loss was an independent prognostic factor for PFS. A three-tier risk prediction model based on four risk factors was established, with 5-year PFS rates of 91.5%, 41.7%, and 34.8% for low-risk, intermediate-risk, and high-risk groups, respectively (P < 0.001). Conclusion: SDHB expression loss and ERBB2 overexpression are adverse prognostic factors in PPGL patients, and there may be a potential link between them. In addition, the risk prediction model established in this study confirms its predictive value for risk stratification in PPGL patients. Significance statement: Studies on the correlation between SDHB expression loss and ERBB2 expression in PPGLs are still in a black stage, and a consensus on risk assessment for PPGL patients has not been reached. Therefore, these two aspects are the key objectives of our research. We investigated SDHB expression loss and ERBB2 expression at the protein level, exploring the correlation between them, conducting prognostic analysis, and establishing a risk model, in order to provide new diagnostic and therapeutic ideas and data support for the clinical management of PPGL patients.
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