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.
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.
Authors: Emmet J Jordan; Hyunjae R Kim; Maria E Arcila; David Barron; Debyani Chakravarty; JianJiong Gao; Matthew T Chang; Andy Ni; Ritika Kundra; Philip Jonsson; Gowtham Jayakumaran; Sizhi Paul Gao; Hannah C Johnsen; Aphrothiti J Hanrahan; Ahmet Zehir; Natasha Rekhtman; Michelle S Ginsberg; Bob T Li; Helena A Yu; Paul K Paik; Alexander Drilon; Matthew D Hellmann; Dalicia N Reales; Ryma Benayed; Valerie W Rusch; Mark G Kris; Jamie E Chaft; José Baselga; Barry S Taylor; Nikolaus Schultz; Charles M Rudin; David M Hyman; Michael F Berger; David B Solit; Marc Ladanyi; Gregory J Riely Journal: Cancer Discov Date: 2017-03-23 Impact factor: 39.397
Authors: J Syrios; N Diamantis; E Fergadis; L Katsaros; M Logothetis; Iota Iakovidou; E Lianos; A Grivas; A E Athanasiou Journal: Med Oncol Date: 2014-06-07 Impact factor: 3.064
Authors: A Adenis; I Ray-Coquard; A Italiano; E Chauzit; B Bui-Nguyen; J-Y Blay; E Tresch-Bruneel; C Fournier; S Clisant; E Y Amela; P A Cassier; M Molimard; N Penel Journal: Br J Cancer Date: 2013-10-22 Impact factor: 7.640
Authors: Armelle Dufresne; Laurent Alberti; Mehdi Brahmi; Sarah Kabani; Héloïse Philippon; David Pérol; Jean Yves Blay Journal: BMC Cancer Date: 2014-08-29 Impact factor: 4.430