Immunohistochemical Studies of Fascin, MMP-9 Overexpression, and Proliferating Index as Prognostic Factors in Cases of a Colon Adenocarcinoma

Kim, Beom Gyu; Ha, Kyung Won; Park, Jun Suk; Yoo, Jae Hyung

Abstract

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-alpha (Topo II-alpha) index. METHODS: Relatively well-preserved paraffin-embedded tissues of 120 cases of colon adenocarcinomas were immunohistochemically stained for fascin, MMP-9, and Topo II-alpha expression. 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-alpha index 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 chi-square test, by using Epi info 2000, for Fascin and/or MMP-9 and a two-sided test for the Topo II-alpha index were employed with a significance of P<0.05. RESULTS: Positive reactions for fascin and MMP-9 in colon adenocarcinomas were 44.2% and 56.7%, respectively. In clinically annotated tumors, fascin immunoreactivity was more common in tumors located in the right colon (P=0.014) and was associated with older age (>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-alpha proliferating 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.