Integrin alpha3 expression as a prognostic factor in colon cancer: association with MRP-1/CD9 and KAI1/CD82.

Recently, we established that a murine monoclonal antibody (MAb) MH8-4 inhibits the motility of the colon cancer cell line RPMI4788 and that it recognizes integrin alpha3. In addition, we have also cloned the motility-related protein-1 (MRP-1)/cluster of differentiation 9 (CD9) as a metastasis suppressor molecule. We investigated integrin alpha3 expression in 114 resected colon cancers using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate whether these experimental results are of relevance in the prognosis of actual colon cancers. Furthermore, we investigated the correlation of integrin alpha3 with MRP-1/CD9 and KAI1/CD82. Sixty patients (52.6%) were evaluated as integrin alpha3-positive and 54 patients (47.4%) as integrin alpha3-negative. Integrin alpha3 expression was associated with tumor status, lymph node status and pathologic stage. The overall and disease-free survival rates for patients whose tumors were positive for integrin alpha3 were significantly higher than for those with integrin alpha3-negative tumors (p < 0.001 and p < 0.001, respectively). This same tendency was observed in node-negative patients (p = 0.007 and p = 0.001, respectively). Integrin alpha3 was found to be the significant prognostic factor in a multivariate analysis using the Cox proportional hazards model (p = 0.036). A correlation was found between integrin alpha3 with MRP-1/CD9 and KAI1/CD82 for stage I tumors. However, no correlation was found in stage III tumors. Our data seem to suggest that low expression of integrin alpha3 is a useful indicator of a poor prognosis for colon cancer patients and that colon cancer progresses following collapse of the complex formed by integrin alpha3 with MRP-1/CD9 and KAI1/CD82.