DCC Gene and Protein Expression in Colorectal Cancer

ABSTRACT

PURPOSE: The germline, or somatic, inactivation of tumor suppressor genes, through point mutation, or deletion, plays an important role in carcinogenesis. Several gene alterations, such as adenomatous polyposis coli (APC), deleted in colorectal cancer (DCC) and p53, have been detected in the development of colorectal cancer. Within these genes, a loss of heterozygosity (LOH) at the DCC gene locus was frequently associated with colorectal tumors, and the LOH of the DCC gene, and the expression of the DCC protein, might be related to malignant formation and metastasis. The aim of this study was to determine the DCC LOH and the expression of DCC protein in colorectal cancers, and evaluate their prognostic value and relationship with the clinicopathological data. MTHODE Fifty colorectal cancer tissues were obtained from resected specimens. Using formalin-fixed paraffin- embedded sections as a source of DNA, we examined the DCC protein in the tissue through immunohistochemical stainings and immunoblotting analysis, the DCC LOH through a polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP). RESULTS: DCC LOH was observed in 24 of the 50 patients (48.0%). The expression of the DCC protein was decreased in the cancer tissue (62.3 23.6%) compared with the adjacent normal mucosa inform the immunoblotting analysis. A decreased DCC protein expression was also observed from the immunohistochemistry, which coincided with the immunoblotting analysis. However, both the DCC LOH and the decreased DCC protein were not related to the clinical and pathological parameters, such as location of tumor, tumor size, histological type and the venous, and lymphatic invasions. There were significant correlations between the DCC protein expression and tumor progression, and hematogenous metastasis (P<.05). CONCLUSIONS: A decreased expression of the DCC protein was noted in human colorectal cancers, and there was a significant relationship between the expression of the DCC protein and distant metastasis, but there was no correlation between the DCC LOH and distant metastasis. These results suggest that the expression of the DCC protein might be related to tumor progression and metastatic potential, and the DCC protein immunoreactivity may be a useful prognostic factor in patients with colorectal cancers.