Local Existence of Osteopontin Positive Tumor-Associated Macrophages in Colorectal Cancer Stroma as Risk Factors of Postoperative Hepatic Metastasis

Eizaburo Ishimaru, Motohiro Imano, Kiyotaka Okuno, Hitoshi Shiozaki and Harumasa Ohyanagi

Department of Surgery, Kinki University School of Medicine

Introduction: Metachronous hepatic metastasis following radical surgery for advanced colorectal cancer has a decisive influence on prognosis, thus screening of high risk patients is important. Osteopontin (OPN) is a phosphorylated glycoprotein with a cell adhesion sequence that is associated with tumor metastasis and proliferation. In the present study, we investigated the relationship between the incidence of hepatic metastasis and OPN expression using a immunohistochemical method in patients with colorectal cancer. Subjects and Methods: Patients with advanced colorectal cancer who underwent radical surgery were divided into 3 groups: those with synchronous hepatic metastasis (n=30), those with metachronous hepatic metastasis (n=17), and nonmetastatic cases (n=54). Immunohistochemical staining was performed using anti-OPN, CD68, and CD105 antibodies. Results: OPN expression was mainly observed in tumor associated macrophages (TAM) that had infiltrated the tumor surrounding the stroma, whereas it was not seen in the tumor cells. The ratios of OPN-positive TAM (OPN/TAM) and microvessel density (MVD) were determined for each location. As a result of univariate analysis in the metachronous hepatic metastasis group, significant differences were observed for the following 3 factors: MVD in the central area of the cancer stroma, and OPN/TAM ratios in the marginal and central areas. Results of multivariate analyses of those 3 suggested that the OPN/TAM ratios in the marginal and central areas of the cancer stroma might be risk factors for metachronous hepatic metastasis. Discussion: We concluded that OPN/TAM ratios in the cancer stroma in the marginal and central areas of excised colorectal specimens are useful for screening patients with a high risk of postoperative hepatic metastasis.

Key words
colorectal cancer, liver metastasis, osteopontin, tumor-associated macrophage

Reprint requests
Motohiro Imano Department of Surgery, Kinki University School of Medicine
377-2 Ohno-higashi, Osaka-sayama, 589-8511 JAPAN

Accepted
January 31, 2007

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