Xi Liqiang, Coello Michael C, Litle Virginia R, Raja Siva, Gooding William E, Yousem Samuel A, El-Hefnawy Talal, Landreneau Rodney J, Luketich James D, Godfrey Tony E
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Clin Cancer Res. 2006 Apr 15;12(8):2484-91. doi: 10.1158/1078-0432.CCR-05-2037.
Occult lymph node metastasis (micrometastasis) is a good prognostic indicator in non-small cell lung cancer (NSCLC) and could be used to direct adjuvant chemotherapy in stage I patients. This study was designed to evaluate molecular markers for detection of occult lymph node metastasis in NSCLC, define the best marker or marker combination to distinguish positive from benign lymph nodes, and evaluate these markers in lymph nodes from pathologically node-negative (pN(0)) NSCLC patients. Potential markers were identified through literature and database searches and all markers were analyzed by quantitative reverse transcription-PCR in a primary screen of six NSCLC specimens and 10 benign nodes. Selected markers were further evaluated on 21 primary NSCLC specimens, 21 positive nodes, and 21 benign nodes, and the best individual markers and combinations were identified. A combination of three markers was further validated on an independent set of 32 benign lymph nodes, 38 histologically positive lymph nodes, and 462 lymph nodes from 68 pN(0) NSCLC patients. Forty-two markers were evaluated in the primary screen and eight promising markers were selected for further analysis. A combination of three markers (SFTPB, TACSTD1, and PVA) was identified that provided perfect classification of benign and positive nodes in all sample sets. PVA and SFTPB are particularly powerful in tumors of squamous and adenocarcinoma histologies, respectively, whereas TACSTD1 is a good general marker for NSCLC metastasis. The combination of these genes identified 32 of 462 (7%) lymph nodes from 20 of 68 (29%) patients as potentially positive for occult metastasis. Long-term follow-up will determine the clinical relevance of these findings.
隐匿性淋巴结转移（微转移）是非小细胞肺癌（NSCLC）的一个良好预后指标，可用于指导I期患者的辅助化疗。本研究旨在评估用于检测NSCLC隐匿性淋巴结转移的分子标志物，确定区分阳性与良性淋巴结的最佳标志物或标志物组合，并在病理淋巴结阴性（pN(0)）的NSCLC患者的淋巴结中评估这些标志物。通过文献和数据库检索确定潜在标志物，并在对6个NSCLC标本和10个良性淋巴结的初步筛查中通过定量逆转录-PCR分析所有标志物。对21个原发性NSCLC标本、21个阳性淋巴结和21个良性淋巴结进一步评估所选标志物，确定最佳的单个标志物和组合。在一组独立的32个良性淋巴结、38个组织学阳性淋巴结和来自68例pN(0) NSCLC患者的462个淋巴结中进一步验证三种标志物的组合。在初步筛查中评估了42种标志物，选择了8种有前景的标志物进行进一步分析。确定了三种标志物（SFTPB、TACSTD1和PVA）的组合，该组合在所有样本集中对良性和阳性淋巴结进行了完美分类。PVA和SFTPB分别在鳞状和腺癌组织学肿瘤中特别有效，而TACSTD1是NSCLC转移的一个良好通用标志物。这些基因的组合将68例患者中的20例（29%）的462个淋巴结中的32个（7%）确定为可能存在隐匿性转移阳性。长期随访将确定这些发现的临床相关性。
