Detection of bone marrow micrometastasis in gastrointestinal cancer patients by immunomagnetic separation

骨髓微转移的检测可以预测肿瘤的广泛传播和预后不良。本研究旨在探讨胃肠道肿瘤患者骨髓微转移检测的临床意义。取53例胃癌患者和52例食管癌患者手术时的骨髓和外周血标本。这些样品通过免疫磁分离富集，并用抗细胞角蛋白抗体进行免疫染色。检测原发性肿瘤中血管内皮生长因子（VEGF）、人表皮生长因子2 （HER2）、细胞周期蛋白D1的表达。胃癌患者骨髓中细胞角蛋白阳性16例（30%），食管癌患者骨髓中细胞角蛋白阳性13例（25%）。骨髓微转移的存在与淋巴结转移（pN）相关，但与肿瘤深度（pT）无关。胃癌骨髓微转移与腹膜播散无相关性。食管癌骨髓微转移患者的累积生存期明显低于无骨髓微转移患者。有骨髓微转移的患者比无骨髓微转移的患者血液循环复发更频繁。局部或播散性复发的患者没有骨髓微转移。骨髓中癌细胞的检测可能是胃肠道肿瘤患者早期血行转移的一个指标。这些患者似乎需要术后强化化疗。

Detection of micrometastasis to the bone marrow can predict widespread disease and a poor prognosis of cancer patients. The purpose of this study was to evaluate the clinical significance of detecting micrometastasis in the bone marrow of gastrointestinal cancer patients. Bone marrow and peripheral blood samples were obtained from 53 gastric and 52 esophageal cancer patients at the time of surgery. These samples were enriched by immunomagnetic separation and immunostained with an anti-cytokeratin antibody. Expression of vascular endothelial growth factor (VEGF) human epidermal growth factor 2 (HER2), and cyclin D1 was examined in the primary tumors. Cytokeratin-positive cancer cells were observed in the bone marrow of 16 (30%) in gastric cancer patients and 13 (25%) in esophageal cancer patients. The presence of bone marrow micrometastasis was correlated with lymph node metastasis (pN) but not associated with depth of tumors (pT). Detection of bone marrow micrometastasis was not associated with peritoneal dissemination in gastric cancer. Cumulative survival of patients with bone marrow micrometastasis was significantly lower than that of patients without it in esophageal cancer. Hematogenous recurrence was more frequent in patients with bone marrow micrometastasis than in those without it. The patients who had local or dissemination recurrence did not have bone marrow micrometastasis. Detection of cancer cells in the bone marrow might be an indicator of early hematogenous metastasis in gastrointestinal cancer patients. Intensive postoperative chemotherapy seems to be indicated for these patients.