title: Stromal Expression of MicroRNA-21 in Advanced Colorectal Cancer Patients with Distant Metastases.
abstract: BACKGROUND
  The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis.
  
  
  METHODS
  miR-21 expression was investigated by using locked nucleic acid- fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry.
  
  
  RESULTS
  The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1-4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041).
  
  
  CONCLUSIONS
  miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Kyu Sang
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Nam
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Koh
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Kang
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Gheeyoung
authors.initials: G
authors.lastname: Choe
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
keywords: Colorectal neoplasms; Genetic heterogeneity; MicroRNA-21; Neoplasm metastasis