Sienel Wulf, Mecklenburg Ingo, Dango Sebastian, Ehrhardt Peter, Kirschbaum Andreas, Passlick Bernward, Pantel Klaus
Department of Thoracic Surgery, Albert-Ludwigs University Freiburg, Freiburg, Germany.
Clin Cancer Res. 2007 Jul 1;13(13):3840-7. doi: 10.1158/1078-0432.CCR-06-2507.
MAGE-A gene expression in humans is mostly restricted to tumor cells, and the role of MAGE-A transcripts and peptides as diagnostic markers and therapeutic targets is currently under investigation. Thus far, the clinical relevance of MAGE-A transcripts as marker for disseminated tumor cells in bone marrow of patients with operable lung cancer without overt metastases is still unclear.
Preoperative bone marrow aspirates from 50 consecutive patients with operable non-small-cell lung cancer free of distant metastases (i.e., pT(1-4) pN(0-2) M(0) R(0)) were admitted to the study. Each bone marrow sample was divided and examined using multimarker MAGE-A reverse transcription-PCR (RT-PCR) and immunocytochemical staining with the anti-pancytokeratin antibody A45-B/B3. Multimarker MAGE-A RT-PCR consisted of multiple subtype-specific nested RT-PCRs with primers for MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, and MAGE-A12. The median follow-up duration was 92 months (range, 18-110 months).
Twenty-six (52%) lung cancer patients harbored MAGE-A transcripts in their bone marrow, as opposed to none of the 30 healthy controls tested. In all 7 patients with immunocytochemically positive bone marrow, MAGE-A transcripts were also detected. All different MAGE-A subtypes (MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, and MAGE-A12) were observed. Sixty-five percent of patients with MAGE-A transcripts in bone marrow exhibited only one subtype. Univariate (P = 0.03, log-rank-test) and multivariate survival analysis showed that MAGE-A transcripts in bone marrow were associated with poor outcome in pN(0) patients (P = 0.02; relative risk, 7.6).
Detection of MAGE-A transcripts in bone marrow predicts an unfavorable outcome in patients with early-stage operable lung cancer. This finding indicates that MAGE-A transcripts are clinically relevant markers of micrometastatic spread in lung cancer and supports further investigation of MAGE-A as potential future therapeutic target.
MAGE - A基因在人类中的表达大多局限于肿瘤细胞，目前正在研究MAGE - A转录本和肽作为诊断标志物及治疗靶点的作用。到目前为止，MAGE - A转录本作为可手术切除且无明显转移的肺癌患者骨髓中播散肿瘤细胞标志物的临床相关性仍不清楚。
连续纳入50例可手术切除的无远处转移的非小细胞肺癌患者（即pT(1 - 4)pN(0 - 2)M(0)R(0)）的术前骨髓抽吸物进行研究。每个骨髓样本进行分割，采用多标志物MAGE - A逆转录聚合酶链反应（RT - PCR）以及抗全细胞角蛋白抗体A45 - B/B3进行免疫细胞化学染色检测。多标志物MAGE - A RT - PCR由针对MAGE - A1、MAGE - A2、MAGE - A3/6、MAGE - A4和MAGE - A12的多个亚型特异性巢式RT - PCR组成。中位随访时间为92个月（范围18 - 110个月）。
26例（52%）肺癌患者的骨髓中存在MAGE - A转录本，而30例健康对照者均未检测到。在所有7例免疫细胞化学检测骨髓呈阳性的患者中，也检测到了MAGE - A转录本。观察到了所有不同的MAGE - A亚型（MAGE - A1、MAGE - A2、MAGE - A3/6、MAGE - A4和MAGE - A12）。骨髓中存在MAGE - A转录本的患者中有65%仅表现为一种亚型。单因素（P = 0.
