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

L. Schirosi, N. Nannini, D. Nicoli, A. Cavazza, R. Valli, S. Buti, L. Garagnani, G. Sartori, F. Calabrese, A. Marchetti, F. Buttitta, L. Felicioni, M. Migaldi, F. Rea, F. Di chiara, M. C. Mengoli, G. Rossi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbermdr626
Pages (from-to)2409-2414
Number of pages6
JournalAnnals of Oncology
Volume23
Issue number9
DOIs
Publication statusPublished - Sep 2012

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Thymoma
Mutation
Exons
Carcinoid Tumor
Squamous Cell Carcinoma
Neuroendocrine Tumors
Neoplasms

Keywords

  • C-KIT
  • Carcinoma
  • CD117
  • Immunohistochemistry
  • Mutation
  • Thymus

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

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, L.; Sartori, G.; Calabrese, F.; Marchetti, A.; Buttitta, F.; Felicioni, L.; Migaldi, M.; Rea, F.; Di chiara, F.; Mengoli, M. C.; Rossi, G.

In: Annals of Oncology, Vol. 23, No. 9, mdr626, 09.2012, p. 2409-2414.

Research output: Contribution to journalArticle

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, MC & Rossi, G 2012, 'Activating c-kit mutations in a subset of thymic carcinoma and response to different c-kit inhibitors', Annals of Oncology, vol. 23, no. 9, mdr626, pp. 2409-2414. https://doi.org/10.1093/annonc/mdr626
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. / Activating c-kit mutations in a subset of thymic carcinoma and response to different c-kit inhibitors. In: Annals of Oncology. 2012 ; Vol. 23, No. 9. pp. 2409-2414.
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abstract = "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.",
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T1 - Activating c-kit mutations in a subset of thymic carcinoma and response to different c-kit inhibitors

AU - Schirosi, L.

AU - Nannini, N.

AU - Nicoli, D.

AU - Cavazza, A.

AU - Valli, R.

AU - Buti, S.

AU - Garagnani, L.

AU - Sartori, G.

AU - Calabrese, F.

AU - Marchetti, A.

AU - Buttitta, F.

AU - Felicioni, L.

AU - Migaldi, M.

AU - Rea, F.

AU - Di chiara, F.

AU - Mengoli, M. C.

AU - Rossi, G.

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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.

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