{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:22:54Z","timestamp":1792174974711,"version":"4.4.0"},"reference-count":50,"publisher":"Bioscientifica","issue":"5","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:p>\n                    Pheochromocytoma and paraganglioma (PPGL) can be divided into at least four molecular subgroups. Whether such categorizations are independent factors for prognosis or metastatic disease is unknown. We performed a systematic review and individual patient meta-analysis aiming to estimate if driver mutation status can predict metastatic disease and survival. Driver mutations were used to categorize patients according to three different molecular systems: two subgroups (\n                    <jats:italic>SDHB<\/jats:italic>\n                    mutated or wild type), three subgroups (pseudohypoxia, kinase signaling or Wnt\/unknown) and four subgroups (tricarboxylic acid cycle,\n                    <jats:italic>VHL\/EPAS1<\/jats:italic>\n                    , kinase signaling or Wnt\/unknown). Twenty-one studies and 703 patients were analyzed. Multivariate models for association with metastasis showed correlation with\n                    <jats:italic>SDHB<\/jats:italic>\n                    mutation (OR 5.68 (95% CI 1.79\u201318.06)) as well as norepinephrine (OR 3.01 (95% CI 1.02\u20138.79)) and dopamine (OR 6.39 (95% CI 1.62\u201325.24)) but not to PPGL location. Other molecular systems were not associated with metastasis. In multivariate models for association with survival, age (HR 1.04 (95% CI 1.02\u20131.06)) and metastases (HR 6.13 (95% CI 2.86\u201313.13)) but neither paraganglioma nor\n                    <jats:italic>SDHB<\/jats:italic>\n                    mutation remained significant. Other molecular subgroups did not correlate with survival. We conclude that molecular categorization accordingly to\n                    <jats:italic>SDHB<\/jats:italic>\n                    provided independent information on the risk of metastasis. Driver mutations status did not correlate independently with survival. These data may ultimately be used to guide current and future risk stratification of PPGL.\n                  <\/jats:p>","DOI":"10.1530\/erc-19-0024","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T08:37:37Z","timestamp":1553071057000},"page":"539-550","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":135,"title":["Genotype\u2013phenotype correlations in pheochromocytoma and paraganglioma: a systematic review and individual patient meta-analysis"],"prefix":"10.1530","volume":"26","author":[{"given":"Joakim","family":"Crona","sequence":"first","affiliation":[{"name":"1Department of Medical Sciences, Uppsala University, Uppsala, Sweden"},{"name":"2Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lamarca","sequence":"additional","affiliation":[{"name":"3Department of Medical Oncology, The Christie NHS Foundation Trust (ENETS Centre of Excellence), Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Ghosal","sequence":"additional","affiliation":[{"name":"2Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan","family":"Welin","sequence":"additional","affiliation":[{"name":"1Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt","family":"Skogseid","sequence":"additional","affiliation":[{"name":"1Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[{"name":"2Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref51","doi-asserted-by":"crossref","first-page":"3974","DOI":"10.1093\/hmg\/ddr324","article-title":"Integrative genomic analysis reveals somatic mutations in pheochromocytoma and paraganglioma","volume":"20","year":"2011","journal-title":"Human Molecular Genetics"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1158\/0008-5472.CAN-17-2463","article-title":"Germline mutations in the mitochondrial 2-oxoglutarate\/malate carrier SLC25A11 gene confer a predisposition to metastatic paragangliomas","volume":"78","year":"2018","journal-title":"Cancer 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