Introduction: Thymic epithelial tumors (TETs) are rare neoplasms with different prognosis lacking consis-tent molecular alterations possibly leading to targeted therapy. We collected a consecutive series of TETsaimed at investigating the mutational status of druggable genes (EGFR, c-KIT, KRAS, BRAF, PDGFR-alphaand −beta, HER2 and c-MET) and the expression of ALK and PD-L1.Patients and methods: One hundred twelve consecutive cases of TETs and relative clinico-pathologic fea-tures were collected. Immunohistochemical expression of ALK (clone D5F3) and PD-L1 (clone E1L3N),molecular analysis of EGFR (exons 18–21), c-KIT (exons 9,11,13,14,17), KRAS (exon 2), BRAF (exon 15),PDGFR-alpha (exon 12) and -beta (exons 12, 14, 18), HER-2 (exons 19 and 20) and c-MET (exons 14,17, 18, 19) mutations were performed. Immuno-molecular results were then statistically matched withclinico-pathologic characteristics.Results: Patients were male in 54% of cases, with a median age of 61 years (range 19–83) and affectedmainly by thymoma (78%) in stage II (45%). At molecular analysis, there were 4 c-KIT mutations (occurringin exon 11 V559A, L576P, Y553N and exon 17 D820E) in thymic carcinomas (type C), but not in other tumortypes (p = 0.003). No mutations were detected in other genes and none case was ALK positive. Twenty-nine (26%) cases were PD-L1 positive (65% of thymic carcinomas and 18% of thymomas). High PD-L1expression was statistically associated with WHO classification stage type C (p < 0.001) and Masaoka stageIII–IV disease (p = 0.007). In univariate analysis, WHO classification type C, advanced Masaoka stage andabsence of myasthenia, but not PD-L1 expressions were correlated with worse survival; at multivariateanalysis, only WHO type C confirmed its negative prognostic role.Conclusion: A subset of TETs as thymic carcinomas can harbor c-KIT mutations and elevated PD-L1 expres-sion that could represent targets of potential therapeutic use.
Analysis of a panel of druggable gene mutations and of ALK and PD-L1 expression in a series of thymic epithelial tumors (TETs) / Tiseo, M; Damato, Angela; Longo, Luigia; Barbieri, F; Bertolini, F; Stefani, Alessandro; Migaldi, M; Gnetti, L; Camisa, R; Bordi, P; Buti, S; Rossi, G. - In: LUNG CANCER. - ISSN 0169-5002. - 104(2017), pp. 24-30. [10.1016/j.lungcan.2016.12.005]
Data di pubblicazione: | 2017 | |
Data di prima pubblicazione: | 14-dic-2016 | |
Titolo: | Analysis of a panel of druggable gene mutations and of ALK and PD-L1 expression in a series of thymic epithelial tumors (TETs). | |
Autore/i: | Tiseo, M; Damato, Angela; Longo, Luigia; Barbieri, F; Bertolini, F; Stefani, Alessandro; Migaldi, M; Gnetti, L; Camisa, R; Bordi, P; Buti, S; Rossi, G | |
Autore/i UNIMORE: | ||
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.lungcan.2016.12.005 | |
Rivista: | ||
Volume: | 104 | |
Pagina iniziale: | 24 | |
Pagina finale: | 30 | |
Codice identificativo ISI: | WOS:000395840900004 | |
Codice identificativo Scopus: | 2-s2.0-85007564293 | |
Codice identificativo Pubmed: | 28212996 | |
Citazione: | Analysis of a panel of druggable gene mutations and of ALK and PD-L1 expression in a series of thymic epithelial tumors (TETs) / Tiseo, M; Damato, Angela; Longo, Luigia; Barbieri, F; Bertolini, F; Stefani, Alessandro; Migaldi, M; Gnetti, L; Camisa, R; Bordi, P; Buti, S; Rossi, G. - In: LUNG CANCER. - ISSN 0169-5002. - 104(2017), pp. 24-30. [10.1016/j.lungcan.2016.12.005] | |
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