Aims: A test predicting distant metastases would be valuable for prognostication in colon cancer (CC). In previous studies, CC with microsatellite instability (MSI) showed a reduced risk of distant metastases. High expression of CD133 and β-catenin, both related to cancer stem cell phenotypes, might be predictive markers for metastasis. The aim of this study was to develop a simple and robust test for risk assessment of distant metastases in CC.
Methods And Results: In a case-control study, 57 cases of right-sided CC specimens with synchronous distant metastases were matched with 57 CC without distant metastases. Immunohistochemistry for MLH1, CD133 and nuclear β-catenin was carried out. To define the diagnostic algorithm the tumours were first stratified according to their MLH1 expression. Loss of MLH1 expression was correlated significantly with a very low risk of distant metastases (5.3%; P = 0.00003). In MLH1-positive cases, combined high scores of CD133 and β-catenin were associated with a very high rate of distant metastases (94.4%), whereas the risk was intermediate for carcinomas with either low CD133 and/or low β-catenin expression (P = 0.0007). A validation study using an independent set of 68 right-sided CC specimens showed a clear trend towards risk stratification according to the algorithm; however, sample sizes were small, and associations were not statistically significant.
Conclusions: By the use of three markers, this algorithm allowed identification of subgroups of right-sided CC patients with extremely high and extremely low risk of distant metastases.
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