title: High tumor cell expression of microRNA-21 in node positive non-small cell lung cancer predicts a favorable clinical outcome.
abstract: BACKGROUND
  MicroRNA (miR)-21 has been revealed as an oncogene in cancer development, and is one of the miRNAs closely connected to angiogenesis. We aimed to explore the impact of miR-21 expression in both tumor and stromal compartments of non-small cell lung cancer (NSCLC), and correlations between miR-21 and angiogenic protein markers.
  
  
  METHODS
  From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). In situ hybridization (ISH) was used to detect the expression of miR-21 separately in tumor cells and stromal cells of the tumor, and immunohistochemistry (IHC) was used to detect the expression of the protein markers protein kinase B (Akt), phosphatidylinositol-3-kinase (PI3K), hypoxia induced factor 1 (HIF1α) and vascular endothelial growth factor-A (VEGF-A).
  
  
  RESULTS
  In univariate analyses, high tumor cell expression of miR-21 in patients with lymph node metastasis was a positive prognostic factor (P = 0.024). High stromal miR-21 expression had a negative prognostic impact (P = 0.022). In the multivariate analysis, low tumor mir-21 expression in node positive patients was an independent adverse prognostic factor (HR 2.03, CI 95% 1.09-3.78, P = 0.027).
  
  
  CONCLUSIONS
  In patients with lymph node metastasis, miR-21 expression in tumor cells is an independent positive prognostic factor. High stromal miR-21 expression is a negative prognostic factor.
authors: Institute of Clinical Medicine, University of Tromso, Tromso, Norway. Helge.Stenvold@uit.no.
authors: Helge
authors: H
authors: Stenvold
authors: Tom
authors: T
authors: Donnem
authors: Sigve
authors: S
authors: Andersen
authors: Samer
authors: S
authors: Al-Saad
authors: Andrej
authors: A
authors: Valkov
authors: Mona Irene
authors: MI
authors: Pedersen
authors: Lill-Tove
authors: LT
authors: Busund
authors: Roy M
authors: RM
authors: Bremnes