Ryan B M, Lefort F, McManus R, Daly J, Keeling P W N, Weir D G, Kelleher D
Department of Clinical Medicine, St James's Hospital, Dublin, Ireland.
Gut. 2003 Jan;52(1):101-8. doi: 10.1136/gut.52.1.101.
Mutant tumour derived DNA has been detected in the sera of colorectal cancer patients. We investigated if mutant serum KRAS2 was detectable preoperatively in a large group of patients with colorectal neoplasia. A prospective study of 94 patients who underwent putative curative resection for colorectal carcinoma (CRC) was performed to ascertain if serum mutant KRAS2 could be used postoperatively as a disease marker.
Preoperative sera from 78 patients were analysed (group A). Sera from 94 patients were obtained three monthly for up to three years during the postoperative period (group B). Codon 12 and 13 KRAS2 mutations were analysed in matched tumour and serum samples.
In the preoperative group (group A), KRAS2 mutation was found in 41/78 (53%) tumours and in 32/78 (41%) preoperative sera. Of 41 tumour KRAS2 mutation positive cases, 31/41 (76%) had an identical serum mutation detectable. In group B, the postoperative follow up group, 60/94 cases were primary tumour KRAS2 mutation positive. Of these 60, 16/60 (27%) became persistently serum mutant KRAS2 positive postoperatively. Ten of 16 (63%) of these developed a recurrence compared with only 1/44 (2%) patients who remained serum mutant negative (odds ratio 71.7 (95% confidence interval 7.7-663.9; p=0.0000). None of 34 tumour mutation negative cases became serum mutant KRAS2 positive postoperatively, despite recurrence in 9/34 patients. The relative hazard of disease recurrence in postoperative serum mutant KRAS2 positive patients was 6.37 (2.26-18.0; p=0.000).
Serum mutant KRAS2 can be detected preoperatively in all stages of colorectal neoplasia. Postoperatively, serum mutant KRAS2 is a strong predictor of disease recurrence, stronger even than Dukes' stage of disease, and thus shows potential for use in clinical practice as a marker of preclinical disease recurrence.
在结直肠癌患者血清中已检测到源自肿瘤的突变DNA。我们调查了在一大群结直肠肿瘤患者中术前是否可检测到血清KRAS2突变。对94例行根治性切除的结直肠癌（CRC）患者进行了一项前瞻性研究，以确定血清突变KRAS2术后能否用作疾病标志物。
分析了78例患者的术前血清（A组）。术后3年内每3个月采集94例患者的血清（B组）。对配对的肿瘤和血清样本分析KRAS2基因第12和13密码子的突变情况。
在术前组（A组），41/78（53%）的肿瘤及32/78（41%）的术前血清中发现KRAS2突变。在41例肿瘤KRAS2突变阳性病例中，31/41（76%）可检测到相同的血清突变。在术后随访组B组中，60/94例患者原发肿瘤KRAS2突变阳性。其中60例中，16/60（27%）术后血清突变KRAS2持续阳性。这16例中的10例（63%）出现复发，而血清突变阴性的44例患者中仅1/44（2%）复发（优势比71.7（95%置信区间7.7 - 663.9；p = 0.0000））。34例肿瘤突变阴性病例术后均未出现血清突变KRAS2阳性，尽管其中9/34例患者复发。术后血清突变KRAS2阳性患者疾病复发的相对风险为6.37（2.26 - 18.0；p = 0.000）。
在结直肠肿瘤的各个阶段术前均可检测到血清突变KRAS2。术后，血清突变KRAS2是疾病复发的有力预测指标，甚至比疾病的Dukes分期更强，因此在临床实践中显示出作为临床前疾病复发标志物的潜力。
