The Experimental Study And Clinical Significance Of K-ras Mutations In Colorectal Cancer

Objective: To investigate the significance of K-ras mutations in various tissues of CRC in the clinical practice.methods: 120 fresh tissues and 173 paraffin-embedded tissues of primary foci, 100 plasma, 67 whole blood, 48 metastatic lymph nodes, 24 metastatic remote organs and 28 colorectal adenoma from CRC patients were screened for Deoxyribonucleic acid (DNA) extraction and K-ras status were examinated by using polymerase chain reaction (PCR) and sequencing analysis.Results: 100% of the fresh primary foci , 97.1% of the paraffin-embedded primary foci,100% of the whole blood and 73.0% of the plasma could be analyzed. The frequency of K-ras mutations in fresh primary foci, paraffin-embedded primary foci, metastatic lymph nodes, metastatic remote organs, plasma, whole blood and colorectal adenoma were 34.2%, 33.9%, 29.8%, 29.2%, 13.7%, 0% and 25.0%. All of the 10 patients with K-ras mutations detected in their plasma were classified into stage D by Dukes'staging. In the samples with a K-ras mutation, 92.5% of the metastatic lymph nodes, 85.7% of the metastatic remote organs, 100.0% of the patients'plasma and 57.1% of the colorectal adenoma had K-ras status consistent with their homologous primary foci. K-ras mutations were found at condon 12 or 13 in 88.8% of the patients, at condon 61 in 3.1% of the patients and at condon 146 in 8.2% of the patients. Codon 12 (GGT→GAT) was the most common mutation. Significantly more male CRC patients than female patients, more eminence type of patients than the ulcer type, more patients older more than 60 years old than the patients less than 60 years old, and more patients with elevated CEA than with normal CEA are likely to have a K-ras mutation in CRC. The frequency of the mutation has no correlation with the pathological histological types, location of tumors, Dukes'stage, or with lymph node or remote metastasis in CRC.Conclusions: Both paraffin-embedded primary foci and fresh primary foci of CRC are suitable for K-ras analysis in clinical practice but patient's whole blood and colorectal adenomain not. Codon 12, codon 13, codon 61 and codon 146 should all be included when K-ras status in CRC were analyzed in clinical practice. The detection of K-ras in patients'plasma for diagnosis is significant only in the patients classified into stage D by Dukes'staging. The results of K-ras analysis from metastatic lymph nodes and metastatic remote organs have some value we can measure when we can not obtain a primary foci sample. The frequency of K-ras mutation in CRC is related to the patient'sex, age, tumor gross morphology and the level of CEA.