{"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":1792174974703,"version":"4.4.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with variable behavior and metastatic potential. Reliable prognostic biomarkers are needed to improve risk stratification and long-term management. Emerging data suggest a role for microRNAs (miRNAs) and immune checkpoint pathways (or inhibitors) in tumor aggressiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the expression of five candidate miRNAs (miR-15a, miR-16, miR-101, miR-183, and miR-483-5p) and programmed death ligand-1 (PD-L1) in PPGL tissues, and assess their associations with clinicopathological features, genetic status and outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective cohort of 130 patients with PPGLs was analyzed, including 53 PPGL tumor and 20 normal adrenal medulla tissues (controls). MiRNA expression was assessed by RT-qPCR in 53 formalin-fixed paraffin-embedded samples (FFPE). PD-L1 and microsatellite instability (MSI) were evaluated by immunohistochemistry in FFPE samples. Associations with tumor type and size, functionality, Ki-67 index, grading scores (PASS, GAPP), metastatic status, localization, and genotype were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 21.5% (28\/130) of patients developed metastases during a median period of follow-up of 45 months and 35 out of the 61 tested (57.4%), harbored pathogenic germline mutations. In tumor samples (n=53), PD-L1 expression was observed in 18.9% (10\/53) whereas no MSI expression was detected. MiR-483-5p was the most consistently upregulated marker in biochemically negative and in high\u2013Ki-67 tumors along with significant up regulation in metastatic PPGL, supporting its role in cellular proliferation and metastatic potential. MiR-183 and miR-101 were overexpressed in pheochromocytomas (PHEOs) with high PASS and Ki-67 indices, while miR-15a and miR-16 displayed higher levels in non-metastatic tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MiR-483-5p emerges as a promising biomarker of aggressive PPGL behavior, while other miRNAs reflect distinct biological behaviors. PD-L1 expression in a subset of cases highlights immune checkpoint inhibition as a potential therapeutic strategy. Prospective validation is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1716806","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T05:16:23Z","timestamp":1764825383000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinicopathological data and the role of miRNA expression in patients with pheochromocytomas\/paragangliomas"],"prefix":"10.3389","volume":"16","author":[{"given":"Foteini","family":"Thanasoula","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria 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