Value of Immunohistochemical Expression of Apelin, Succinate Dehydrogenase B, Chromogranin B, Human Epidermal Growth Factor Receptor-2, Contactin 4, and Succinyl-CoA Synthetase Subunit Beta in Differentiating Metastatic From Non-Metastatic Pheochromocytoma and Paraganglioma

Wang, Yong; Chen, Danlei; Pang, Yingxian; Xu, Xiaowen; Guan, Xiao; Liu, Longfei

doi:10.3389/fendo.2022.882906

Cited by 4 publications

(6 citation statements)

References 49 publications

(55 reference statements)

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“…Previous studies which performed SDHB IHC also showed that the loss of SDHB protein is associated with poor prognosis ( 30 , 32 ), and they discovered that patients with SDHB (-) tumors had considerably lower OS and DFS than those with SDHB (+) tumors. Compared to the research mentioned above, our study had a larger sample size and a longer follow-up time.…”

Section: Discussionmentioning

confidence: 96%

“…Recent studies have shown that SDHB protein loss can be used as an IHC biomarker to independently predict the prognosis of PCC/PGL patients ( 30 – 32 ), and a modified GAPP system (M-GAPP) and COPPs scoring system also incorporates loss of SDHB staining for analyzing PCC/PGL risk ( 18 , 33 ). Despite these above studies have included SDHB IHC in the investigation of the prognosis of PCC/PGL, no reliable prospective study or long-term follow-up for PCC/PGL focusing on SDHB IHC is available at present.…”

Section: Introductionmentioning

confidence: 99%

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SDHB immunohistochemistry for prognosis of pheochromocytoma and paraganglioma: A retrospective and prospective analysis

Yang

Jiang

et al. 2023

Front. Endocrinol.

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IntroductionPheochromocytomas and paragangliomas (PCC/PGL) are rare neuroendocrine tumors and can secrete catecholamine. Previous studies have found that SDHB immunohistochemistry (IHC) can predict SDHB germline gene mutation, and SDHB mutation is closely associated with tumor progression and metastasis. This study aimed to clarify the potential effect of SDHB IHC as a predictive marker for tumor progression in PCC/PGL patients.MethodsWe included PCC/PGL patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from 2002 to 2014 for retrospective analysis and discovered that SDHB (-) staining patients had poorer prognoses. Then we examined SDHB protein expression by IHC on all tumors in the prospective series, which was composed of patients from 2015 to 2020 in our center.ResultsIn the retrospective series, the median follow-up was 167 months, and during follow-up, 14.4% (38/264) patients developed metastasis or recurrence, and 8.0% (22/274) patients died. Retrospective analysis revealed that 66.7% (6/9) of participants in the SDHB (-) group and 15.7% (40/255) of those in the SDHB (+) group developed progressive tumors (OR: 10.75, 95% CI: 2.72-52.60, P=0.001), and SDHB (-) was independently associated with poor outcomes after adjusting by other clinicopathological parameters (OR: 11.68, 95% CI: 2.58-64.45, P=0.002). SDHB (-) patients had shorter disease-free survival (DFS) and overall survival (OS) (P<0.001) and SDHB (-) was significantly associated with shorter median DFS (HR: 6.89, 95% CI: 2.41-19.70, P<0.001) in multivariate cox proportional hazard analysis. In the prospective series, the median follow-up was 28 months, 4.7% (10/213) patients developed metastasis or recurrence, and 0.5% (1/217) patient died. For the prospective analysis, 18.8% (3/16) of participants in the SDHB (-) group had progressive tumors compared with 3.6% (7/197) in the SDHB (+) group (RR: 5.28, 95% CI: 1.51-18.47, P=0.009), statistical significance remained (RR: 3.35, 95% CI: 1.20-9.38, P=0.021) after adjusting for other clinicopathological factors.ConclusionsOur findings demonstrated patients with SDHB (-) tumors had a higher possibility of poor outcomes, and SDHB IHC can be regarded as an independent biomarker of prognosis in PCC/PGL.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

SDHB immunohistochemistry for prognosis of pheochromocytoma and paraganglioma: A retrospective and prospective analysis

Yang

Jiang

et al. 2023

Front. Endocrinol.

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“…It is worth noting that CNTN4 has been found overexpressed at the mRNA level in malignant PCPG comparing with benign 15 . However, there is no significant difference in protein expression of CNTN4 between benign and malignant PCPG in immunohistochemistry 16 . The abnormal expression of SH3GL2 is mainly related to the pathogenesis of Parkinson's disease, as well as the migration and invasion behaviors of glioblastoma and triple‐negative breast cancer 17–19 .…”

Section: Discussionmentioning

confidence: 96%

“…15 However, there is no significant difference in protein expression of CNTN4 between benign and malignant PCPG in immunohistochemistry. 16 The abnormal expression of SH3GL2 is mainly related to the pathogenesis of Parkinson's disease, as well as the migration and invasion behaviors of glioblastoma and triple-negative breast cancer. [17][18][19] In the present study, the expression of…”

Section: Identification Of the Prognostic Markersmentioning

confidence: 99%

Clinicopathological characteristics of pheochromocytoma/paraganglioma and screening of prognostic markers

Lei

Cha

et al. 2023

Journal of Surgical Oncology

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BackgroundMalignant pheochromocytoma/paraganglioma (PCPG) is lethal and difficult to diagnose before metastasis. This study is aiming to characterize the PCPG and explore novel prognostic markers.MethodsClinical data of patients with pathologically confirmed invasive and noninvasive PCPG were collected and analyzed. Then, the differentially expressed genes (DEGs) and HUB genes were identified by R package “limma” in GSE67066‐GPL570. Afterward, the prognostic markers were screened out using R packages of “survival” and “survminer” based on the TCGA data.ResultsThe 34 invasive PCPGs were characterized by irregular contour and unclear boundary on CT and capsule/extracapsule tissue invasion on pathology compared with the 42 noninvasive PCPGs. Then, 29 upregulated and 30 downregulated DEGs were identified in malignant PCPG compared with benign, which were mainly enriched in the terms of calcium ion binding, neuron cell–cell adhesion, axon, regulation of hormone levels, and regulation of secretion by cell. Of which, nine DEGs were furtherly selected as the HUB genes. Finally, CNTN4 and SH3GL2 were found to be highly expressed in malignant PCPGs and negatively correlated with progression‐free interval.ConclusionsMalignant PCPGs tend to be aggressive in imaging and pathology. The high expression of CNTN4 and SH3GL2 in PCPGs may indicate a poor prognosis.

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“…The expression of human telomerase reverse transcriptase (hTERT) and heat shock protein 90 (HSP90) is higher in metastatic tumors [ 58 ]. Other markers such as chromogranin B and S100 protein have been associated with nonmetastatic tumor behavior [ 23 , 38 , 59-63 ].…”

mentioning

confidence: 99%

Identification of Predictors of Metastatic Potential in Paragangliomas to Develop a Prognostic Score (PSPGL)

Iguchi,

Martins Filho,

Soares

et al. 2024

Journal of the Endocrine Society

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Context Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5-35% of PGLs and there are no reliable predictors of metastatic disease. Objective To develop a prognostic score of metastatic potential in PGLs. Methods Retrospective analysis of clinical data of a cohort with PGL and tumor histological assessment. Patients were divided into metastatic PGL (presence of metastasis) and non-metastatic PGL (absence of metastasis ≥96 months of follow up) groups. Univariate and multivariate analysis were performed to identify predictors of metastatic potential. A prognostic score was developed based on coefficients of multivariate analysis. Kaplan Meier curves were generated to estimate Disease Specific Survival (DSS). Results Out of 263 patients, 35 patients had metastatic PGL and 110 patients had non-metastatic PGL. In multivariate analysis, four features were independently related to metastatic disease and composed the Prognostic Score of Paragangliomas (PSPGL): presence of central or confluent necrosis (33 points), > 3 mitosis/10 high power field (HPF) (28 points), extension into adipose tissue (20 points) and extra-adrenal location (19 points). PSPGL ≥24 showed similar sensitivity with higher specificity than Pheochromocytoma of the Adrenal gland Scaled Score (PASS) and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). PSPGL ≤ 20 was associated with risk of metastasis of ∼10% whereas PSPGL ≥ 40 was associated with ∼80%. The presence of metastasis and Ki-67 ≥ 3% were related to lower DSS. Conclusion PSPGL, composed of four easy-to-assess parameters, demonstrated good performance in predicting metastatic potential and good ability in estimate metastasis risk.

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Value of Immunohistochemical Expression of Apelin, Succinate Dehydrogenase B, Chromogranin B, Human Epidermal Growth Factor Receptor-2, Contactin 4, and Succinyl-CoA Synthetase Subunit Beta in Differentiating Metastatic From Non-Metastatic Pheochromocytoma and Paraganglioma

Cited by 4 publications

References 49 publications

SDHB immunohistochemistry for prognosis of pheochromocytoma and paraganglioma: A retrospective and prospective analysis

SDHB immunohistochemistry for prognosis of pheochromocytoma and paraganglioma: A retrospective and prospective analysis

Clinicopathological characteristics of pheochromocytoma/paraganglioma and screening of prognostic markers

Identification of Predictors of Metastatic Potential in Paragangliomas to Develop a Prognostic Score (PSPGL)

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