To analyze a multi-institutional series of type C thymic carcinomas (TCs) (including neuroendocrine tumors), focusing on the expression and mutations of c-KIT. 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. 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.

Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors / Schirosi, L; Nannini, N; Nicoli, D; Cavazza, A; Valli, R; Buti, S; Garagnani, Lorella; Sartori, G; Calabrese, F; Marchetti, A; Buttitta, F; Felicioni, L; Migaldi, Mario; Rea, F; Di Chiara, F; Mengoli, Mc; Rossi, G.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - STAMPA. - 23:9(2012), pp. 2409-2414. [10.1093/annonc/mdr626]

Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors.

GARAGNANI, Lorella;MIGALDI, Mario;
2012

Abstract

To analyze a multi-institutional series of type C thymic carcinomas (TCs) (including neuroendocrine tumors), focusing on the expression and mutations of c-KIT. 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. 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.
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Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors / Schirosi, L; Nannini, N; Nicoli, D; Cavazza, A; Valli, R; Buti, S; Garagnani, Lorella; Sartori, G; Calabrese, F; Marchetti, A; Buttitta, F; Felicioni, L; Migaldi, Mario; Rea, F; Di Chiara, F; Mengoli, Mc; Rossi, G.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - STAMPA. - 23:9(2012), pp. 2409-2414. [10.1093/annonc/mdr626]
Schirosi, L; Nannini, N; Nicoli, D; Cavazza, A; Valli, R; Buti, S; Garagnani, Lorella; Sartori, G; Calabrese, F; Marchetti, A; Buttitta, F; Felicioni, L; Migaldi, Mario; Rea, F; Di Chiara, F; Mengoli, Mc; Rossi, G.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/707785
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