Pellisé Maria, Castells Antoni, Ginès Angels, Agrelo Rubén, Solé Manel, Castellví-Bel Sergi, Fernández-Esparrach Glòria, Llach Josep, Esteller Manel, Bordas Josep M, Piqué Josep M
Department of Gastroenterology, Institut de Malalties Digestives, Centre de Diagnòstic Biomèdic, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Catalonia, Spain.
Clin Cancer Res. 2004 Jul 1;10(13):4444-9. doi: 10.1158/1078-0432.CCR-03-0600.
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.
内镜超声引导下细针穿刺抽吸术（EUS-FNA）已成为胃肠道和肺癌分期的基本操作。然而，越来越多的证据表明，淋巴结中存在微转移，而标准病理方法无法检测到这些微转移。本研究的目的是评估通过EUS-FNA从淋巴结获取的样本进行高甲基化基因启动子分析是否可行，并确定该策略在检测胃肠道和非小细胞肺癌患者微转移方面的实用性。对连续的食管癌、胃癌、直肠癌和非小细胞肺癌患者，根据EUS检查结果对可疑淋巴结进行EUS-FNA采样。通过甲基化特异性PCR对MGMT、p16(INK4a)和p14(ARF)基因启动子CpG岛进行高甲基化分析。就明确诊断而言，确定了传统细胞学、甲基化分析及其联合使用的有效性。纳入了27例患者，共42个淋巴结（食管癌11个、直肠癌7个、胃癌3个、肺癌21个）。根据明确诊断，21个（50%）为转移性淋巴结。传统细胞学的敏感性、特异性和总体准确率分别为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，两种技术联合使用提高了敏感性（90%），但降低了特异性（67%）。总之，通过高甲基化基因启动子分析在EUS-FNA样本中检测隐匿性肿瘤细胞是可行的。此外，在传统细胞学中加入甲基化分析可能会提高其敏感性，但会以降低特异性为代价。
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