Annals of oncology : official journal of the European Society for Medical Oncology · 2012
Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Schirosi L, Nannini N, Nicoli D, Cavazza A, Valli R, Buti S, Garagnani L, Sartori G, Calabrese F, Marchetti A, Buttitta F, Felicioni L, Migaldi M, Rea F, Di Chiara F, Mengoli M C, Rossi G
Аннотация
BACKGROUND: To analyze a multi-institutional series of type C thymic carcinomas (TCs) (including neuroendocrine tumors), focusing on the expression and mutations of c-KIT.
MATERIALS AND METHODS: Immunohistochemical expression of c-KIT/CD117, p63, CD5 and neuroendocrine markers, as well as mutational analysis of c-KIT exons 9, 11, 13, 14, 17 by direct sequencing of 48 cases of TCs. Immunohistochemical and molecular data were statistically crossed with clinicopathological features.
RESULTS: Overall, 29 tumors (60%) expressed CD117, 69% were positive for CD5 and 85% (41 cases) for p63. Neuroendocrine markers stained all six atypical carcinoids and five poorly-differentiated thymic squamous cell carcinomas. Overall, six CD117-positive cases (12.5%) showed c-KIT mutation. No mutation was detected in CD117-negative tumors and carcinoids. All the mutations were found in poorly-differentiated thymic squamous cell carcinomas expressing CD117, CD5, p63 and lacking neuroendocrine markers (6 of 12 cases with these features). Mutations involved exon 11 (four cases: V559A, L576P, Y553N, W557R), exon 9 (E490K) and exon 17 (D820E).
CONCLUSIONS: All TCs need an immunohistochemical screening with CD117, while c-KIT mutation analysis is mandatory only in CD117-positive cases, particularly when coexpressing CD5 and p63, lacking neuroendocrine differentiation. The finding of c-KIT mutation can predict efficacy with different c-KIT inhibitors.
MATERIALS AND METHODS: Immunohistochemical expression of c-KIT/CD117, p63, CD5 and neuroendocrine markers, as well as mutational analysis of c-KIT exons 9, 11, 13, 14, 17 by direct sequencing of 48 cases of TCs. Immunohistochemical and molecular data were statistically crossed with clinicopathological features.
RESULTS: Overall, 29 tumors (60%) expressed CD117, 69% were positive for CD5 and 85% (41 cases) for p63. Neuroendocrine markers stained all six atypical carcinoids and five poorly-differentiated thymic squamous cell carcinomas. Overall, six CD117-positive cases (12.5%) showed c-KIT mutation. No mutation was detected in CD117-negative tumors and carcinoids. All the mutations were found in poorly-differentiated thymic squamous cell carcinomas expressing CD117, CD5, p63 and lacking neuroendocrine markers (6 of 12 cases with these features). Mutations involved exon 11 (four cases: V559A, L576P, Y553N, W557R), exon 9 (E490K) and exon 17 (D820E).
CONCLUSIONS: All TCs need an immunohistochemical screening with CD117, while c-KIT mutation analysis is mandatory only in CD117-positive cases, particularly when coexpressing CD5 and p63, lacking neuroendocrine differentiation. The finding of c-KIT mutation can predict efficacy with different c-KIT inhibitors.
Предметные рубрики MeSH
AdultAgedAged, 80 and overAntineoplastic AgentsBenzamidesBenzenesulfonatesCD5 AntigensCarcinoid TumorCarcinoma, Squamous CellDNA Mutational AnalysisEnzyme ActivationFemaleGenetic Association StudiesHumansImatinib MesylateIndolesMaleMiddle AgedMutation, MissenseNiacinamidePhenylurea CompoundsPiperazinesProto-Oncogene Proteins c-kitPyridinesPyrimidinesPyrrolesRetrospective StudiesSorafenibSunitinibThymomaThymus NeoplasmsTranscription FactorsTreatment OutcomeTumor Suppressor Proteins