Purpose: The malignant conversion of epithelial cells involves alterations in the expression and the function of cell-matrix and cell-cell adhesive systems that enable a switch to a migratory phenotype in tumor invasion and metastasis. Here, the author studies the prevalence and the potential clinical significance of fascin and Matrix metalloproteinase-9 (MMP-9) expression in relation to the progression of colon adenocarcinoma and of tumor cell proliferation as measured by using the topoisomerase II-α(Topo II-α ) index. Methods: Relatively well-preserved paraffin-embedded tissues of 120 cases of colon adenocarcinomas were immunohistochemically stained for fascin, MMP-9, and Topo II-αexpression. A reaction was determined as being positive when more than 10% of the cells were positive for fascin, and/or MMP-9. The Topo II-αindex is defined as the positive number of tumor cells divided by the total number of tumor cells counted times 100. At least 1,000 cells were counted for this analysis. A χ 2 test, by using Epi info 2000, for Fascin and/or MMP-9 and a two-sided test for the Topo II-αindex were employed with a significance of P 65 yr, P=0.028), tumor grading (P=0.009), and lymph node metastases (P=0.005). However, MMP-9 immunoreactivity was not statistically associated with age, gender, tumor stage, or lymph node metastases. Fascin expression was statistically associated with MMP-9 expression, especially for left colon adenocarcinomas (P=0.0032). Although the topo II- αproliferating index was associated with lymph node metastasis (P<0.01), this result was not statistically associated with Fascin or MMP-9 expression. Conclusion: Fascin expression may be closely linked with tumor grading and lymph node metastasis of more aggressive colon adenocarcinomas and partly associated with MMP-9 expression in tumor invasion. However, further studies of fascin expression as an independent prognostic factor are required for the determination of significant relationships with other clinicopathologic indices.