TY - JOUR
T1 - C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma
AU - Rivera, Rosario S.
AU - Nagatsuka, Hitoshi
AU - Gunduz, Mehmet
AU - Cengiz, Beyhan
AU - Gunduz, Esra
AU - Siar, Chong Huat
AU - Tsujigiwa, Hidetsugu
AU - Tamamura, Ryo
AU - Han, Kok Ng
AU - Nagai, Noriyuki
N1 - Funding Information:
Acknowledgments This work was supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology (B17406027, C19592109). The authors would also like to thank Ms. Kazuko Funakoshi for her technical expertise. The experiments complied with the current laws of Japan.
PY - 2008/1
Y1 - 2008/1
N2 - C-kit is a trans-membrane receptor tyrosine kinase (RTK) encoded by the proto-oncogene KIT located at 4q11-12. Gain-of-function mutations arising to c-kit activation independent of its ligand were observed in various tumors related to germ cells, mast cells, and interstitial cells of Cajal. C-kit also participates in melanocyte development; hence, its involvement in oral mucosal melanoma (OMM) tumorigenesis was investigated. Immunohistochemistry and mutation analysis were performed using 18 cases of human primary OMM. Results revealed 16 cases positive to c-kit protein. Atypical melanocytes expressed c-kit. All in situ components expressed c-kit, but only four cases exhibited intense expression in the invasive component. Missense mutations were observed in four cases, and two of those correlated with increased protein expression. C-kit expression in atypical melanocytes suggests the role of c-kit in the early stage of OMM tumorigenesis. C-kit protein expression correlated with activating mutations indicating the pertinent role of the proto-oncogene KIT in the tumorigenesis of OMM.
AB - C-kit is a trans-membrane receptor tyrosine kinase (RTK) encoded by the proto-oncogene KIT located at 4q11-12. Gain-of-function mutations arising to c-kit activation independent of its ligand were observed in various tumors related to germ cells, mast cells, and interstitial cells of Cajal. C-kit also participates in melanocyte development; hence, its involvement in oral mucosal melanoma (OMM) tumorigenesis was investigated. Immunohistochemistry and mutation analysis were performed using 18 cases of human primary OMM. Results revealed 16 cases positive to c-kit protein. Atypical melanocytes expressed c-kit. All in situ components expressed c-kit, but only four cases exhibited intense expression in the invasive component. Missense mutations were observed in four cases, and two of those correlated with increased protein expression. C-kit expression in atypical melanocytes suggests the role of c-kit in the early stage of OMM tumorigenesis. C-kit protein expression correlated with activating mutations indicating the pertinent role of the proto-oncogene KIT in the tumorigenesis of OMM.
KW - C-kit mutation
KW - Immunohistochemistry
KW - Oral mucosal melanoma
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U2 - 10.1007/s00428-007-0524-2
DO - 10.1007/s00428-007-0524-2
M3 - Article
C2 - 18066592
AN - SCOPUS:37549021543
VL - 452
SP - 27
EP - 32
JO - Virchows Archiv - Abteilung A Pathologische Anatomie
JF - Virchows Archiv - Abteilung A Pathologische Anatomie
SN - 0945-6317
IS - 1
ER -