Lloyd Julia M, McIver Cassandra M, Stephenson Sally-Anne, Hewett Peter J, Rieger Nicholas, Hardingham Jennifer E
Department of Haematology-Oncology, Hetzel Institute, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville, SA 5011, Australia.
Clin Cancer Res. 2006 Jan 15;12(2):417-23. doi: 10.1158/1078-0432.CCR-05-1473.
Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse.
We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin gamma2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse.
Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors.
The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer.
被诊断为I期或II期疾病的结直肠癌患者在原发性肿瘤切除后通常不进行辅助化疗。然而，高达10%的I期患者和30%的II期患者在术后5年内会因复发性或转移性疾病而复发。本研究的目的是确定肿瘤相关标志物是否能够检测到播散性恶性细胞，从而识别出具有复发风险的早期结直肠癌患者亚组。
我们招募了连续接受早期结直肠癌根治性切除的患者。使用免疫磁珠逆转录聚合酶链反应检测五种肿瘤相关标志物（癌胚抗原、层粘连蛋白γ2、 Ephrin B4、基质溶解素和细胞角蛋白20），以检测结肠癌患者围手术期外周血和腹腔内是否存在结肠肿瘤细胞。使用Kaplan-Meier方法在单变量分析中测试临床病理变量对生存结果的影响。进行多变量Cox比例风险回归分析，以确定肿瘤细胞的检测是否是疾病复发的独立预后标志物。
总体而言，125例早期患者中有41例（32.8%）播散性肿瘤细胞呈阳性。切除后灌洗样本中播散性细胞标志物呈阳性的患者预后明显较差（风险比，6.2；95%置信区间，1.9 - 19.6；P = 0.002），且这与其他风险因素无关。
本研究中使用的标志物识别出了一组原发性结直肠癌切除术后复发风险增加的早期患者亚组。该方法可被视为一种新的诊断工具，以改善结直肠癌的分期和管理。
