Detection of lymph node micrometastases by gene promoter hypermethylation in samples obtained by endosonography-guided fine-needle aspiration biopsy
Detection of lymph node micrometastases by gene promoter hypermethylation in samples obtained by endosonography-guided fine-needle aspiration biopsy
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DOI：
10.1158/1078-0432.ccr-03-0600
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发表时间：
2004-07-01
影响因子：
11.5
通讯作者：
Piqué, JM
中科院分区：
文献类型：
--
作者：
Pellisé, M;Castells, A;Piqué, JM
内镜下超声引导下细针穿刺（EUS-FNA）已成为胃肠道和肺癌分期的基本程序。然而，越来越多的证据表明，微转移存在于淋巴结中，这是标准病理方法无法检测到的。本研究的目的是评估高甲基化基因启动子分析是否适用于EUS-FNA从淋巴结获得的样本，并确定该策略在胃肠道和非小细胞肺癌患者微转移检测中的有效性。通过EUS- fna对连续的食管癌、胃癌、直肠癌和非小细胞肺癌患者的EUS检查结果进行可疑淋巴结取样。通过甲基化特异性PCR对MGMT、p16（INK4a）和p14（ARF）基因启动子CpG岛进行超甲基化分析。常规细胞学、甲基化分析及其联合诊断的有效性被确定。纳入27例患者，共42个淋巴结（食管癌11例，直肠癌7例，胃癌3例，肺癌21例）。根据明确诊断，21例（50%）对应转移性淋巴结。常规细胞学的敏感性、特异性和总体准确性分别为76%、100%和88%，而甲基化分析的相应值分别为81%、67%和74%。与传统细胞学相比，两种技术的结合增加了灵敏度（90%），但降低了特异性（67%）。综上所述，利用超甲基化基因启动子分析检测EUS-FNA样品中隐匿性肿瘤细胞是可行的。此外，在常规细胞学中加入甲基化分析可能会以降低特异性为代价增加其敏感性。
Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become a fundamental procedure for gastrointestinal and lung cancer staging. However, there is growing evidence that micrometastases are present in lymph nodes, which cannot be detected with standard pathological methods. The aim of this study was to evaluate whether hypermethylation gene promoter analysis was feasible on samples obtained by EUS-FNA from lymph nodes, as well as to establish the usefulness of this strategy for the detection of micrometastases in patients with gastrointestinal and non-small cell lung cancer.Suspicious lymph nodes based on EUS findings from consecutive patients with esophageal, gastric, rectal, and non-small cell lung cancer were sampled by EUS-FNA. Hypermethylation analysis of the MGMT,p16(INK4a), and p14(ARF) gene promoter CpG islands were performed by methylation-specific PCR. Effectiveness of conventional cytology, methylation analysis, and their combination were established with respect to the definitive diagnosis.Twenty-seven patients were included, thus representing a total of 42 lymph nodes (esophageal cancer, n = 11; rectal cancer, n = 7; gastric cancer, n = 3; and lung cancer, n = 21). According to definitive diagnosis, 21 (50%) corresponded to metastatic lymph nodes. Sensitivity, specificity, and overall accuracy of conventional cytology were 76%, 100%, and 88%, respectively, whereas the corresponding values for the methylation analysis were 81%, 67%, and 74%, respectively. Combination of both techniques increased sensitivity (90%) but decreased specificity (67%) with respect to conventional cytology.In conclusion, it is feasible to detect occult neoplastic cells in EUS-FNA samples by hypermethylation gene promoter analysis. Moreover, addition of methylation analysis to conventional cytology may increase its sensitivity at the expenses of a decrease in its specificity.