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• W2553037175 abstract "Context Paragangliomas and pheochromocytomas (PPGLs) exhibit variable malignancy, which is difficult to determine by histopathology, amine measurements or tissue genetic analyses. Objective To evaluate whether a 51-neuroendocrine gene blood analysis has clinical utility as a diagnostic and prognostic marker. Design Prospective cohort study. Well-differentiated PPGLs ( n = 32), metastatic ( n = 4); SDHx mutation ( n = 25); 12 biochemically active, Lanreotide treated ( n = 4). Nine patients had multiple sampling. Age- and gender-matched controls and GEP-NETs (comparators). Methods Circulating neuroendocrine tumor mRNA measured (qPCR) with multianalyte algorithmic analysis. Metabolic, epigenomic and proliferative genes as well as somatostatin receptor expression were assessed (averaged, normalized gene expression: mean ± s.e.m. ). Amines were measured by HPLC and chromogranin A by ELISA. Analyses (2-tailed): Fisher’s test, non-parametric (Mann–Whitney), receiver-operator curve (ROC) and multivariate analysis (MVA). All data are presented as mean ± s.e.m . Results PPGL were NETest positive (100%). All exhibited higher scores than controls (55 ± 5% vs 8 ± 1%, P = 0.0001), similar to GEP-NETs (47 ± 5%). ROC analysis area under curve was 0.98 for differentiating PPGLs/controls (cut-off for normal: 26.7%). Mutation status was not directly linked to NETest. Genetic and molecular clustering was associated ( P < 0.04) with NETest scores. Metastatic (80 ± 9%) and multicentric (64 ± 9%) disease had significantly ( P < 0.04) higher scores than localized disease (43 ± 7%). Progressive disease (PD) had the highest scores (86 ± 2%) vs stable (SD, 41 ± 2%) ( P < 0.0001). The area under the curve for PD from SD was 0.93 (cut-off for PD: 53%). Proliferation, epigenetic and somatostatin receptor gene expression was elevated ( P < 0.03) in PD. Metabolic gene expression was decreased in SDHx mutations. Repeat NETest measurements defined clinical status in the 9 patients (6 SD and 3 PD). Amine measurement was non-informative. Multivariate analysis identified NETest >53% as an independent prognostic factor. Conclusion Circulating NET transcript analysis is positive (100% diagnostic) in well-differentiated PCC/PGL, scores were elevated in progressive disease irrespective of mutation or biochemical activity and elevated levels were prognostic." @default.
• W2553037175 created "2016-11-30" @default.
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• W2553037175 date "2017-02-01" @default.
• W2553037175 modified "2023-10-18" @default.
• W2553037175 title "The clinical utility of circulating neuroendocrine gene transcript analysis in well-differentiated paragangliomas and pheochromocytomas" @default.
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• W2553037175 doi "https://doi.org/10.1530/eje-16-0727" @default.
• W2553037175 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27913608" @default.
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