KIT (CD117) Expression in a Subset of Non-Small Cell Lung Carcinoma (NSCLC) Patients

Albert D. Donnenberg, Ludovic Zimmerlin, Rodney J. Landreneau, James D. Luketich, Vera S. Donnenberg

Research output: Contribution to journalArticle

Abstract

We have previously described the expression of CD44, CD90, CD117 and CD133 in NSCLC tumors, adjacent normal lung, and malignant pleural effusions (MPE). Here we describe the unique subset of tumors expressing CD117 (KIT), a potential therapeutic target. Tumor and adjacent tissue were collected from 58 patients. Six MPE were obtained before therapy. Tissue was paraffin embedded for immunofluorescent microscopy, disaggregated and stained for flow cytometry or cryopreserved for later culture. The effect of imatinib on CD117high/KIT+ tumors was determined on first passage cells; absolute cell counts and flow cytometry were readouts for drug sensitivity of cell subsets. Primary tumors divided into KITneg and KIT+ by immunofluorescence. By more sensitive flow cytometric analysis, CD117+ cytokeratin+ cells were detected in all tissues (1.1% of cytokeratin+ cells in normal lung, 1.29% in KIT "negative" tumors, 40.7% in KIT+ tumors, and 0.4% in MPE). In KIT+/CD117high, but not KIT+/CD117low tumors, CD117 was overexpressed 3.1-fold compared to normal lung. Primary cultures of CD117high tumors were sensitive to imatinib (5 μM) in short term culture. We conclude that NSCLC tumors divide into CD117low and CD117high. Overexpression of CD117 in CD117high NSCLC supports exploring KIT as a therapeutic target in this subset of patients.

Original languageEnglish (US)
Article numbere52885
JournalPLoS One
Volume7
Issue number12
DOIs
StatePublished - Dec 20 2012
Externally publishedYes

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Non-Small Cell Lung Carcinoma
carcinoma
Tumors
lungs
Cells
neoplasms
Neoplasms
Malignant Pleural Effusion
cells
Flow cytometry
Tissue
Keratins
Lung
therapeutics
flow cytometry
Flow Cytometry
Paraffin
alkanes
fluorescent antibody technique
Fluorescent Antibody Technique

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Donnenberg, A. D., Zimmerlin, L., Landreneau, R. J., Luketich, J. D., & Donnenberg, V. S. (2012). KIT (CD117) Expression in a Subset of Non-Small Cell Lung Carcinoma (NSCLC) Patients. PLoS One, 7(12), [e52885]. https://doi.org/10.1371/journal.pone.0052885

KIT (CD117) Expression in a Subset of Non-Small Cell Lung Carcinoma (NSCLC) Patients. / Donnenberg, Albert D.; Zimmerlin, Ludovic; Landreneau, Rodney J.; Luketich, James D.; Donnenberg, Vera S.

In: PLoS One, Vol. 7, No. 12, e52885, 20.12.2012.

Research output: Contribution to journalArticle

Donnenberg, Albert D. ; Zimmerlin, Ludovic ; Landreneau, Rodney J. ; Luketich, James D. ; Donnenberg, Vera S. / KIT (CD117) Expression in a Subset of Non-Small Cell Lung Carcinoma (NSCLC) Patients. In: PLoS One. 2012 ; Vol. 7, No. 12.
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