title: c-kit expression in adenocarcinomas of the lung.
abstract: The tyrosine-kinase receptor c-kit (CD117) and its ligand stem cell factor are considered to be co-expressed in various solid tumors, including adenocarcinomas of the lung. The frequency of c-kit expression and its association with clinical parameters has not yet been evaluated in a larger population of lung adenocarcinomas. Therefore, tumor tissue of 95 consecutive patients with adenocarcinoma of the lung was stained using a polyclonal c-kit antibody. c-kit expression was correlated with relevant clinical parameters obtained by chart review. Positive c-kit expression in tumor tissue was observed in 61 of 95 patients (64%). Univariate analysis showed a significant effect of T (p = 0.003), N (p = 0.001) and M stage (p < 0.001) as well as of performance status (p = 0.001), surgical resection (p < 0.001), and LDH serum levels (p = 0.016) on survival. In contrast, c-kit protein expression was non- significant (p = 0.913). However, multivariate Cox regression with the influential parameters revealed a significant effect of c-kit expression on survival. Forward stepwise selection showed a 1.77-fold increased risk to die (hazard ratio, HR; 95% confidence interval, CI: 1.00-3.14, p = 0.047) for patients with c-kit-positive tumors. Similar data for c-kit expression were obtained by backward stepwise selection (HR: 1.78; 95% CI: 1.00-3.16; p = 0.044). In conclusion, the receptor tyrosine kinase c-kit is frequently expressed in adenocarcinomas of the lung and has a relevant effect on patient survival. The results of this study support clinical trials targeting the c-kit receptor with specific c-kit inhibitors (e.g. imatinib).
authors.affiliation: Institute of Legal Medicine and Rudolf Boehm Institute of Pharmacology and Toxicology, Leipzig, Germany. patrick.micke@licr.uu.se
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.forename: Jan Georg
authors.initials: JG
authors.lastname: Hengstler
authors.forename: Heidi
authors.initials: H
authors.lastname: Albrecht
authors.forename: Andreas
authors.initials: A
authors.lastname: Faldum
authors.forename: Fernando
authors.initials: F
authors.lastname: Bittinger
authors.forename: Kai
authors.initials: K
authors.lastname: Becker
authors.forename: Rainer
authors.initials: R
authors.lastname: Wiewrodt
authors.forename: Berthold
authors.initials: B
authors.lastname: Fischer
authors.forename: Roland
authors.initials: R
authors.lastname: Buhl
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D019009:Proto-Oncogene Proteins c-kit