The prognostic importance of miRNA-21 in stage II colon cancer: A population-based study.

Abstract

3513 Background: Adjuvant chemotherapy for stage II colon cancer patients is still controversial and the debate on which patients should be considered as high risk patients is still ongoing. The decision is based on clinical and pathological markers of risk, which are inadequately informative in most of the patients, and better methods are highly needed. The aim of the present study was to investigate the possible prognostic importance of miRNA-21, quantified by in situ hybridization (ISH), in a unique, large population-based cohort of patients treated for stage II colon cancer patients. Methods: The study included all patients diagnosed with stage II colon cancer in Denmark in the year 2003 (711 patients), representing a full population of five million people. Patients receiving adjuvant chemotherapy were excluded (N=15). One paraffin-embedded tissue block was obtained from each patient. A 6μm-thick section was processed for formazan-based chromogenic miR-21 ISH analysis and counter stained with nuclear red. The blue miR-21 ISH signal was assessed by image analysis to obtain two quantitative expression estimates: the total blue area (TB) and the ratio of TB with the nuclear density (TBR). Results: The miRNA-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. Patients expressing high levels of miRNA-21 (high mean TBR) had significantly inferior cancer specific survival (CSS): HR = 1.26 (95% CI; 1.15-1.60), p <0.001. In the COX regression analysis (including; gender, T-category, malignancy grade, localization, tumor perforation, tumor fixation, number of lymph nodes and MSI status), mean TBR was found to be an independent predictive marker of poor CSS, HR = 1.41 (95%CI; 1.19-1.67, p< 0.001). The same applied to TB. Conclusions: The present study shows that increasing miRNA-21 expression level is significantly correlated to decreasing CSS. Analyses of miRNA-21 should be considered as a potential adjunct in the selection of high risk stage II patients.