J Pathol Transl Med.  2016 Jul;50(4):270-277. 10.4132/jptm.2016.03.19.

Stromal Expression of MicroRNA-21 in Advanced Colorectal Cancer Patients with Distant Metastases

• Lee KS
• Nam SK
• Koh J
• Kim DW
• Kang SB
• Choe G
• Kim WH
• Lee HS

• KMID: 2345549
• DOI: http://doi.org/10.4132/jptm.2016.03.19

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.

Keyword

Colorectal neoplasms; MicroRNA-21; Neoplasm metastasis; Genetic heterogeneity

MeSH Terms

Actins
Colorectal Neoplasms*
Desmin
Fibroblasts
Fluorescence
Genetic Heterogeneity
Humans
Immunohistochemistry
In Situ Hybridization
Neoplasm Metastasis*
Population Characteristics
Prognosis
Actins
Desmin

Figure

• 

  Fig. 1. MicroRNA-21 (miR-21) staining using locked nucleic acid–based in situ hybridization in colorectal cancer. (A) miR-21 expression is observed in cancer stromal tissue. (B) No miR-21 expression is observed in normal colonic mucosa.

• 

  Fig. 2. Kaplan-Meier curves illustrating the overall survival of patients with advanced colorectal cancer in relation to microRNA-21 expression. (A) Center. (B) Periphery. (C) Distant metastasis.

• 

  Fig. 3. Correlation between microRNA-21 (miR-21) expression and cancer associated fibroblasts (CAFs) by Mann-Whitney analysis. (A) Center. (B) Periphery. (C) Distant metastasis. CI, confidence interval.

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