DETECTION OF CIRCULATING TUMOR-CELLS IN COLORECTAL-CANCER BY IMMUNOBEAD-PCR IS A SENSITIVE PROGNOSTIC MARKER FOR RELAPSE OF DISEASE
DETECTION OF CIRCULATING TUMOR-CELLS IN COLORECTAL-CANCER BY IMMUNOBEAD-PCR IS A SENSITIVE PROGNOSTIC MARKER FOR RELAPSE OF DISEASE
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DOI：
10.1007/bf03401893
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发表时间：
1995-11-01
影响因子：
5.7
通讯作者：
DOBROVIC, A
中科院分区：
文献类型：
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作者：
HARDINGHAM, JE;KOTASEK, D;DOBROVIC, A
背景资料：结直肠癌的复发和转移仍然是一个主要问题，根治性切除术后5年的生存率仍然只有约50%。此外，高达70%的早期疾病患者也会复发并在5年内死亡，这表明诊断时存在微转移性疾病。转移性扩散的一种途径是通过血流，因此血液中肿瘤细胞的检测可能提供关于疾病复发的重要预测工具。我们已经开发出一种敏感的分子技术，以确定在血液中的肿瘤细胞使用的K-ras基因作为marker.Materials和方法的密码子12突变：27例肿瘤进行了研究，在围手术期外周血样本中的肿瘤细胞的存在下，在K-ras基因的密码子12突变。用上皮特异性抗体标记的免疫磁珠用于从血液中收获上皮细胞。K-ras基因突变被确定在这个选定的人口使用聚合酶链反应（PCR）为基础的分析（免疫珠-PCR）。结果：循环K-ras基因突变的细胞中检测到的27例患者中的9个，这9例患者中有7人已经死亡，由于复发或转移性疾病。在18名患者中未检测到突变细胞，18名患者中有16名保持无病（中位随访时间：16个月;范围：7-42个月）。Kaplan-Meier分析显示血液中K-ras突变细胞的chat检测与无病生存率显著降低相关（p = 0.0001）。结论：本研究表明，通过免疫珠-PCR检测围手术期循环肿瘤细胞为复发和转移性结直肠癌提供了一个敏感的预后指标。
Background: Recurrent and metastatic carcinoma of the colorectum remains a major problem, with survival at 5 years post curative resection still only about 50%. Moreover, up to 70% of patients who present with early stage disease also relapse and die within 5 years, suggesting the presence of micrometastatic disease at diagnosis. One route of metastatic spread is via the blood stream, hence the detection of tumor cells in blood is likely to provide an Important predictive tool with respect to relapse of disease. We have developed a sensitive molecular technique to identify tumor cells in blood using mutations in codon 12 of the K-ras gene as a marker.Materials and Methods: Twenty-seven patients whose tumor carried a mutation in codon 12 of K-ras were studied for the presence of tumor cells in perioperative peripheral blood samples. Immunomagnetic beads, labeled with an epithelial-specific antibody, were used to harvest epithelial cells from blood. K-ras mutations were identified in this selected population using a polymerase chain reaction (PCR)-based analysis (immunobead-PCR).Results: Circulating K-ras mutant cells were detected in 9 of 27 patients; seven of these nine patients have since died due to recurrent or metastatic disease. Mutant cells were not detected in 18 patients, and 16 of 18 have remained disease free (median follow-up: 16 months; range: 7-42 months). Kaplan-Meier analysis showed chat detection of K-ras mutant cells in blood was associated with significantly reduced disease-free survival (p = 0.0001).Conclusion: This study indicates that detection of circulating tumor cells perioperatively by immunobead-PCR provides a sensitive prognostic marker for recurrent and metastatic colorectal cancer.