Prognostic Impact Of Cdx2 In Stage Ii Colon Cancer: Results From Two Nationwide Cohorts.

3610 Background: The aim of the present study was to validate the prognostic impact of CDX2 in stage II colon cancer and confirm its clinical potential. Methods: Individual patient data and formalin fixed, paraffin embedded tumor tissue were collected from two unbiased, population-based cohorts representing all patients operated for stage II colon cancer in Denmark in 2002 and 2003. The CDX2 expression was evaluated by immunohistochemistry on whole tumor sections. Patients were classified into three groups, of CDX2 expression: positive, intermediate, and negative, for comparison with the clinical data. The endpoint was disease free survival (DFS). Results: A total of 1,157 patients was included. We found a significant relationship between loss of CDX2 expression and poor DFS in both cohorts, p = 0.0267 and p = 0.0118, respectively. Five-year DFS rates were 66%, 72%, and 74% in the test cohort and 62%, 65%, and 75% in the validation cohort for the negative, intermediate, and positive CDX2 expressing groups, respectively. Multiple Cox regression analysis performed on the combined cohorts confirmed an independent prognostic impact of CDX2 on DFS, hazard ratio 1.543 (95% confidence interval 1.129-2.108), p = 0.0065. CDX2 loss was also associated with an adverse prognosis in patients with tumors harboring microsatellite instability (MSI) (p = 0.0001). Tumors with focal loss of CDX2 expression in the budding cells constituted a specific group with a very poor prognosis, demonstrating a 5-year DFS of only 60%. Conclusions: The present study provides further strong evidence regarding prognostic impact of CDX2 in patients with stage II colon cancer. CDX2 expression should be considered when deciding on adjuvant chemotherapy, especially in the group of patients with MSI tumors.