Low Levels of Insulin-Like Growth Factor Type 1 Receptor Expression at Cancer Cell Membrane Predict Liver Metastasis in Dukes’ C Human Colorectal Cancers
| Autor: | Michio Nakamura, Takahiro Hasebe, Masahiro Asaka, Hiroyuki Maeda, Takafumi Sangai, Atsushi Ochiai, Genichiro Ishii, Shin'ichi Miyamoto, Shi-chuan Zhang, Yasushi Endoh, Norio Saito |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Colorectal cancer medicine.medical_treatment Receptor expression Adenocarcinoma Receptor IGF Type 1 Metastasis Insulin-like growth factor Biomarkers Tumor medicine Carcinoma Humans Neoplasm Invasiveness Aged Neoplasm Staging Aged 80 and over business.industry Cell Membrane Liver Neoplasms Middle Aged Prognosis medicine.disease Adenocarcinoma Mucinous Primary tumor Survival Rate Oncology Carcinoma Squamous Cell Cancer research Female Neoplasm Recurrence Local Colorectal Neoplasms business Immunostaining Follow-Up Studies |
| Zdroj: | Clinical Cancer Research. 10:8434-8441 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-04-0430 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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