Molecular detection of occult cancer cells in sentinel lymph node of gastrointestinal and breast cancer

决定为乳腺癌患者提供全身辅助治疗取决于预期获益（改善无复发生存率和总生存率）和预期风险（不良反应）之间的平衡。腋窝淋巴结受累强烈预测早期复发，并被广泛认为是辅助治疗的指征。淋巴结阴性患者的预后通常更好，并且在初次手术后通常不接受进一步治疗。然而，在日本，这些患者中约有10%至15%发生远处转移，最终死于疾病。许多临床随机试验已经产生了新的证据，原发性乳腺癌的辅助治疗的疗效。分子技术的最新发展，包括聚合酶链反应（PCR），现在允许敏感检测外周血中的循环肿瘤细胞。由于癌胚抗原（CEA）mRNA在包括癌细胞在内的几乎所有上皮细胞中都能检测到，而在非上皮细胞中却不能检测到，因此有研究者将CEA作为靶基因。在血液样品中检测到的CEA mRNA意味着存在血源性上皮细胞，推测为癌细胞。考虑到这一背景，我们前瞻性地研究了100例接受淋巴结阴性乳腺癌根治性手术的连续患者，以测试通过CEA mRNA RT-PCR检测外周血中的肿瘤细胞是否是预后指标。术前样本中CEA mRNA阳性的患者生存率低于CEA mRNA阴性的患者。在术前和术后样本中，CEA mRNA表达的患者生存率最低。术前和术后血液样本中CEA mRNA的分子检测是接受根治性手术的淋巴结阴性乳腺癌患者的独立阴性预后因素。

The decision to offer systemic adjuvant therapy to a patient with breast cancer depends on the balance between expected benefit (improved relapse-free and overall survival) and expected risk (adverse effects). Involvement of axillary lymph nodes strongly predicts early relapse, and is widely considered an indication for adjuvant therapy. Node-negative patients generally have a more favorable prognosis, and often receive no further treatment after the primary operation. However, in Japan, distant metastases develop in approximately 10% to 15% of these patients, who ultimately die of their disease. Many clinical randomized trials have generated new evidence of efficacy of adjuvant therapy for primary breast cancer. Recent developments in molecular technology including the polymerase chain reaction (PCR) now permit sensitive detection of circulating tumor cells in peripheral blood. Several researchers have used carcinoembryonic antigen (CEA) as the target gene because CEA mRNA can be detected in almost all epithelial cells including cancer cells, but not in nonepithelial cells. CEA mRNA detected in blood samples implies the presence of blood-borne epithelial cells, presumably cancer cells. Considering this background, we prospectively studied 100 consecutive patients undergoing curative surgery for node-negative breast cancer to test whether tumor cell detection in peripheral blood by CEA mRNA RT-PCR was a prognostic indicator. Patients with CEA mRNA in preoperative samples had poorer survival than those with no detectable CEA mRNA. The worst survival rate was seen in those with CEA mRNA in both pre-and postoperative samples. Molecular detection of CEA mRNA in both pre-and postoperative blood samples is an independent negative prognostic factor in patients with node-negative breast cancer undergoing curative surgery.