title: Histological specificity of alterations and expression of KIT and KITLG in non-small cell lung carcinoma.
abstract: Characterization of molecules within important oncogenetic pathways may have future implications for development of therapies and biomarkers in lung cancer. One such target is the tyrosine kinase receptor KIT (c-KIT). We evaluated alterations and expression of KIT and its ligand, KITLG (also known as SCF), in 72 clinical lung tumor specimens of different histologies. Gene copy number, mRNA expression levels, and protein expression were assayed using array-based comparative genomic hybridization, real-time quantitative reverse transcription PCR and immunohistochemistry, respectively. For validation, we investigated copy number alterations and mRNA expression in external microarray data sets of 1,600 and 555 primary lung tumors, respectively. Positivity for KIT staining was most common in large cell neuroendocrine carcinoma (LCNEC) which also showed the highest KIT mRNA expression levels whereas expression was lowest in squamous cell carcinoma (SqCC). KIT mRNA expression levels were higher in KIT immunopositive samples, but expression was not affected by KIT copy numbers. Copy number gains of KIT were significantly more frequent in SqCC compared with adenocarcinoma in our own series and in the 1,600-sample data set. Immunopositivity for both KIT and KITLG in the same tumor was rare except in LCNEC. Our results highlight an increased KIT mRNA expression and frequent KIT immunopositivity in LCNEC but point out a poor correlation between KIT copy numbers and expression in SqCC, perhaps reflecting the existence of a protective mechanism against KIT alterations in this subgroup.
authors.affiliation: Division of Oncology, Department of Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Annette
authors.initials: A
authors.lastname: Salomonsson
authors.forename: Mats
authors.initials: M
authors.lastname: Jönsson
authors.forename: Sofi
authors.initials: S
authors.lastname: Isaksson
authors.forename: Anna
authors.initials: A
authors.lastname: Karlsson
authors.forename: Per
authors.initials: P
authors.lastname: Jönsson
authors.forename: Alexander
authors.initials: A
authors.lastname: Gaber
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Leif
authors.initials: L
authors.lastname: Johansson
authors.forename: Hans
authors.initials: H
authors.lastname: Brunnström
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.forename: Åke
authors.initials: Å
authors.lastname: Borg
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.forename: Maria
authors.initials: M
authors.lastname: Planck
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000235:genetics*; D016019:Survival Analysis; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit