Detection of DCC and Ki-ras gene alterations in colorectal carcinoma tissue as prognostic markers for liver metastatic recurrence

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Abstract
The mortality of patients with colorectal carcinoma depends mainly upon subsequent liver metastasis even after curative operation. However, it is very difficult to predict the incidence of liver metastasis by analyzing conventional tumor markers or pathologic findings. In the current study, the authors examined the genetic alterations of p53/DCC loci and Ki-ras in colorectal carcinoma in relation to liver metastasis, and investigated whether these gene alterations could be prognostic markers for liver metastasis. Primary tumor tissue samples were collected at surgery from 30 patients with no liver metastasis and 24 patients with liver metastasis. Among the 30 patients with no liver metastasis at surgery, 9 developed liver metastasis after surgery. After the extraction of DNA, we investigated the loss of heterozygosity at p53/DCC loci and mutations of Ki-ras codon 12 in the colorectal carcinoma tissue from these patients. The incidence of allelic loss of the DCC locus was significantly greater for patients with liver metastasis that for patients who had no liver metastasis for more than 2 years (19/20:95% vs 2/5:40%, P < 0.05). However, mutations of Ki-ras codon 12 were significantly less in patients with liver metastasis than in patients with no liver metastasis for more than 2 years (6/33:18% vs 6/11:55%, P < 0.05). The current study indicated that detection of allelic loss of DCC and absence of Ki-ras codon 12 mutations are associated with the metastatic potential of colorectal carcinoma in the liver. These results suggested that these gene alterations might be reliable biologic markers for assessing the potential of liver metastasis after colorectal resection.