Thebo J S, Senagore A J, Reinhold D S, Stapleton S R
Ferguson-Blodgett Digestive Disease Institute, Grand Rapids, Michigan, USA.
Dis Colon Rectum. 2000 Feb;43(2):155-9; discussion 159-62. doi: 10.1007/BF02236973.
Multiple attempts have been made to improve the clinical/pathologic staging system of Dukes to focus adjuvant therapy decisions. The purpose of this study was to determine whether K-ras mutational status of regional nodes in patients with Dukes B2 colorectal cancer could be used to stage their disease more accurately.
Using formalin-fixed, paraffin-embedded archival material, tumor samples were screened for K-ras mutations using a mutation-specific polymerase chain reaction method, followed by gel electrophoresis in a 96-well array. Patients with Dukes B2 tumors that have mutations in codon 12 or 13 of the K-ras gene were identified.
Mutational analysis of the lymph nodes from these patients revealed an 80 percent (16/20) incidence of the same mutations in regional lymph nodes. None of the four patients with mutation-free nodes developed recurrence compared with 37.5 percent (6/16) with K-ras positive lymph nodes.
The data suggest that patients with Dukes B2 colorectal cancers that have mutations in codon 12 or 13 of the K-ras gene are at high risk for the development of nodal metastases. Mutational analysis of the lymph nodes identifies high-risk patients who should be considered for adjuvant chemotherapy. Therefore, K-ras mutational analysis should be considered for molecular staging of colorectal cancer.
人们多次尝试改进杜克分期系统以指导辅助治疗决策。本研究旨在确定杜克B2期结直肠癌患者区域淋巴结的K-ras突变状态是否可用于更准确地对其疾病进行分期。
使用福尔马林固定、石蜡包埋的存档材料，采用突变特异性聚合酶链反应方法对肿瘤样本进行K-ras突变筛查，随后在96孔阵列中进行凝胶电泳。确定患有K-ras基因第12或13密码子突变的杜克B2期肿瘤患者。
对这些患者淋巴结的突变分析显示，区域淋巴结中相同突变的发生率为80%（16/20）。4例淋巴结无突变的患者均未复发，而K-ras阳性淋巴结患者的复发率为37.5%（6/16）。
数据表明，K-ras基因第12或13密码子发生突变的杜克B2期结直肠癌患者发生淋巴结转移的风险较高。对淋巴结进行突变分析可识别出应考虑接受辅助化疗的高危患者。因此，K-ras突变分析应被纳入结直肠癌的分子分期考量。
