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Low Levels of Insulin-Like Growth Factor Type 1 Receptor Expression at Cancer Cell Membrane Predict Liver Metastasis in Dukes’ C Human Colorectal Cancers

¹ Pathology Division, National Cancer Center Research Institute East and ² Department of Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; and ³ Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Purpose: The aim of this study was to evaluate the prognostic significance of insulin-like growth factor type 1 receptor (IGF-1R) expression in Dukes’ C human colorectal cancers (CRCs).

Experimental Design: Immunohistochemical staining for IGF-1R was done on formalin-fixed, paraffin-embedded specimens from 161 patients with curatively resected Dukes’ C CRC and at least 5-year follow-up periods. We investigated the association between the levels of IGF-1R expression and the clinicopathologic parameters. To evaluate the accurate prognostic value of IGF-1R expression, we investigated two patterns of recurrence-free survival (RFS) according to the mode of recurrence, the hepatic-RFS (H-RFS), and the nonhepatic-RFS (nH-RFS). The influence of the pattern of IGF-1R immunostaining (membranous or cytoplasmic) on RFS was also estimated.

Results: High (diffuse staining) and low (focal staining) levels of IGF-1R expression were found in 45 (28%) and 116 (72%) specimens, respectively. The recurrence rate was significantly higher in the latter group (49 of 116) than the former group (9 of 45; P = 0.01). H-RFS was significantly longer for the former group than the latter group (P = 0.021), whereas no difference was found in nH-RFS between the two groups (P = 0.121). In multivariate analysis, the level of IGF-1R expression was an independent factor for H-RFS (P = 0.015) as were the depth of invasion and lymph vessel invasion (P = 0.006 and 0.022, respectively). Using a combination of the level of IGF-1R expression and these two factors, the prognostic value was further increased. When IGF-1R staining patterns (membranous or cytoplasmic) were compared, membrane staining of IGF-1R possessed prognostic significance.

Conclusions: In Dukes’ C CRC, focal membrane expression of IGF-1R in the primary tumor can predict a high risk of recurrence, especially liver metastasis. Understanding the mechanisms involved could lead to new therapeutic approaches for advanced CRC.

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