Osteopontin Induced by Macrophages Contribute to Metachronous Liver Metastases in Colorectal Cancer

Even after radical surgery for stage II and stage III colorectal cancer, metachronous liver metastasis is frequently observed. The aim of this study was to identify the risk of metachronous liver metastasis with retrospective clinicopathological study. Immunohistochemistry was performed to evaluate the expression of Osteopontin (OPN), CD-68, and CD105 in 41 cases of stage II and stage III colorectal cancer tissue. Stage II and stage III colorectal cancer patients who had undergone R0 resection were classified into two groups: with metachronous liver metastasis (m-LM; n = 17) and without liver metastases (control; n = 24). Additionally, double-immunofluorescence staining was performed using antibodies to OPN and CD68. OPN-positive cells were frequently colocalized with CD68 immunoreactivity. OPN and microvascular density expression in the central area were significantly higher in the m-LM (OPN; control 4.3 ± 0.56, m-LV 10.8 ± 1.48, P < 0.05; microvascular density control 18.5 ± 2.86, m-LV 31.4 ± 4.39, P < 0.05), while CD68 expression in the invasive margin was significantly higher in the control group (control 98.9 ± 7.31, m-LV 28.2 ± 3.18, P < 0.05). These results suggest that the risk of metachronous liver metastasis could be well predicted by immunohistochemical staining of OPN in the central areas, and CD68 in the invasive margins of tumors.