TY - JOUR
T1 - High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients
AU - Nielsen, Boye Schnack
AU - Jørgensen, Stine
AU - Fog, Jacob Ulrik
AU - Søkilde, Rolf
AU - Christensen, Ib Jarle
AU - Hansen, Ulla
AU - Brunner, Nils
AU - Baker, Adam
AU - Møller, Søren
AU - Nielsen, Hans Jørgen
PY - 2011/1
Y1 - 2011/1
N2 - Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The miR-21 signal was revealed as a blue chromogenic reaction, predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. The expression levels were measured using image analysis. The miR-21 signal was determined as the total blue area (TB), or the area fraction relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06-1.55) in the stage II colon cancer patient group, whereas no significant correlation with disease-free survival was observed in the stage II rectal cancer group. In multivariate analysis both TB and TBR estimates were independent of other clinical parameters (age, gender, total leukocyte count, K-RAS mutational status and MSI). We conclude that miR-21 is primarily a stromal microRNA, which when measured by image analysis identifies a subgroup of stage II colon cancer patients with short diseasefree survival.
AB - Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The miR-21 signal was revealed as a blue chromogenic reaction, predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. The expression levels were measured using image analysis. The miR-21 signal was determined as the total blue area (TB), or the area fraction relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06-1.55) in the stage II colon cancer patient group, whereas no significant correlation with disease-free survival was observed in the stage II rectal cancer group. In multivariate analysis both TB and TBR estimates were independent of other clinical parameters (age, gender, total leukocyte count, K-RAS mutational status and MSI). We conclude that miR-21 is primarily a stromal microRNA, which when measured by image analysis identifies a subgroup of stage II colon cancer patients with short diseasefree survival.
KW - Former LIFE faculty
KW - MicroRNA
KW - MiR-21
KW - Colorectal cancer
KW - In situ hybridization
KW - LNA
U2 - 10.1007/s10585-010-9355-7
DO - 10.1007/s10585-010-9355-7
M3 - Journal article
C2 - 21069438
SN - 0262-0898
VL - 28
SP - 27
EP - 38
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 1
ER -
