{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:08:59Z","timestamp":1770332939594,"version":"3.49.0"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Un Respiro per la Vita E.T.S"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Thymomas are the most common tumors of the anterior mediastinum. While early-stage disease often has a favorable prognosis, therapeutic options in advanced stages remain limited. Moreover, the molecular profile of thymomas is still poorly characterized. In the present study, we explored the presence of targetable mutations and programmed death-ligand 1 (PD-L1) expression in a cohort of surgically resected thymomas. Furthermore, we investigated the correlation between PD-L1 expression, histological subtype, and risk of recurrence in patients who underwent curative-intent thymectomy. Methods: Mutational profiling was performed using a DNA-based NGS Cancer Panel of 16 genes. PD-L1 expression was evaluated via Tumor Proportion Score (TPS), and thymomas with TPS \u2265 50% were identified as high expressors. The associations with histological subtype and disease-free survival (DFS) were analyzed using logistic regression, Cox proportional hazards models, and Kaplan\u2013Meier survival curves. Results: In our study, 2\/37 (5.4%) of tested neoplasms (type AB and B2 thymoma) reported as a PIK3CA mutation; no other targetable mutations were observed. Moreover, high PD-L1 expression (\u226550%) was reported in (15\/37) 40.5% of patients and was significantly associated with aggressive histological subtypes (B2 and B3) (p &lt; 0.001). Logistic regression analysis showed that high PD-L1 expression was a significant predictor of aggressive histology (McFadden\u2019s R2 = 0.268, p &lt; 0.001), with an odds ratio of 15.5 (95% CI: 2.9\u201383.4; p = 0.001). During follow-up, 5\/37 (13.5%) of patients experienced disease recurrence; however, no significant difference in DFS was found between high and low PD-L1 expression groups. Conclusions: Our data confirm the presence of PIK3CA mutations in thymomas and encourage the exploration the potential role of molecular target therapy in this setting. Moreover, we underlined that high PD-L1 expression level is associated with more aggressive thymoma subtypes and may have a role as a prognostic biomarker. These findings support the need for further studies on the potential role of molecular and predictive pathology in thymic epithelial tumors.<\/jats:p>","DOI":"10.3390\/diagnostics16030484","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T11:13:01Z","timestamp":1770289981000},"page":"484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Landscape of Resected Thymomas: Insights from Mutational Profiling"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-5107","authenticated-orcid":false,"given":"Luca","family":"Frasca","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1048-6625","authenticated-orcid":false,"given":"Antonio","family":"Sarubbi","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"},{"name":"Master\u2019s Degree Program in Medicine and Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo, 21, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-0596","authenticated-orcid":false,"given":"Lorenzo","family":"Nibid","sequence":"additional","affiliation":[{"name":"Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo, 21, 00128 Rome, Italy"},{"name":"Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5648-011X","authenticated-orcid":false,"given":"Ilaria","family":"Suriano","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-1684","authenticated-orcid":false,"given":"Filippo","family":"Longo","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6841-1610","authenticated-orcid":false,"given":"Giovanna","family":"Sabarese","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8014-6779","authenticated-orcid":false,"given":"Daniela","family":"Righi","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9538-5729","authenticated-orcid":false,"given":"Giuseppe","family":"Perrone","sequence":"additional","affiliation":[{"name":"Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo, 21, 00128 Rome, Italy"},{"name":"Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1509-6714","authenticated-orcid":false,"given":"Pierfilippo","family":"Crucitti","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ejca.2007.11.004","article-title":"Thymic epithelial tumours: A population-based study of the incidence, diagnostic procedures and therapy","volume":"44","author":"Blaauwgeers","year":"2008","journal-title":"Eur. 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