Prognostic Impact of SOX9 in Stage II Colon Cancer: Results from a Large Nationwide Cohort.

183 Background: Up-regulation of the transcription factor SOX9 has been described in colon cancer, and it has been argued that differences in the expression levels dictates cell proliferation. The aim of the present study was to analyze the prognostic impact of SOX9 in patients with stage II colon cancer. Methods: Individual patient data and formalin fixed paraffin embedded tumor tissue were collected from a large unbiased, population-based cohort, representing all patients operated for stage II colon cancer in Denmark in 2002 and 2003. The SOX9 expression was evaluated by immunohistochemistry on whole tumor sections. Patients were classified into three groups dependent on the SOX9 expression gradient in the tumor: luminal, peripheral, and uniform for comparison with the clinical data. The endpoint was disease free survival (DFS). Results: A total of 1,153 patients were included. We detected an expression-dependent relationship between SOX9 and prognosis. Patients with tumors exhibiting a luminal expression pattern (N = 267, increasing SOX9 expression towards the luminal compartment of the tumor) were characterized by a significantly better DFS compared to the uniform (N = 846) and peripheral (N = 40) patterns, p = 0.0070. The five-year DFS rates were 74%, 67%, and 56%, respectively. Multiple Cox regression analysis, confirmed an independent prognostic advantage of the luminal SOX9 expression pattern, as compared to the uniform pattern, hazard ratio (HR) 0.7211 (95% confidence interval (CI) 0.5561-0.9351), p = 0.0137, whereas the possible disadvantage of the periphery pattern could not be verified, p = 0.1405. Conclusions: The present results support a prognostic impact of SOX9 in stage II colon cancer. The consequence of an altered SOX9 expression seems to differ between intra-tumoral compartments, and we propose that a gradient-dependent evaluation should be applied to provide the most clinically relevant information about this transcription factor.