Braun S, Schlimok G, Heumos I, Schaller G, Riethdorf L, Riethmüller G, Pantel K
Frauenklinik & Poliklinik, Klinikum rechts der Isar, Technische Universität, München, Germany.
Cancer Res. 2001 Mar 1;61(5):1890-5.
Occult hematogenous micrometastases are the major cause for metastatic relapse and cancer-related death in patients with operable primary breast cancer. Although sensitive immunocytochemical and molecular methods allow detection of individual breast cancer cells in bone marrow (BM), a major site of metastatic relapse, current detection techniques cannot discriminate between nonviable shed tumor cells and seminal metastatic cells. To address this problem, we analyzed the relevance of erbB2 overexpression on disseminated cytokeratin-18-positive breast cancer cells in the BM of 52 patients with locoregionally restricted primary breast cancer using immunocytochemical double labeling with monoclonal antibody 9G6 to the p185erbB2 oncoprotein. Expression of p185erbB2 on BM micrometastases was detected in 31 of 52 (60%) patients independent of established risk factors such as lymph node involvement, primary tumor size, differentiation grade, or expression of p185erbB2 on primary tumor cells. After a median follow-up of 64 months, patients with p185erbB2-positive BM micrometastases had developed fatal metastatic relapses more frequently than patients with p185erbB2-negative micrometastases (21 versus 7 events; P = 0.032). In multivariate analysis, the presence of p185erbB2-positive micrometastases was an independent prognostic factor with a hazard ratio of 2.78 (95% confidence interval, 1.11-6.96) for overall survival (P = 0.029). We therefore conclude that erbB2 overexpression characterizes a clinically relevant subset of breast cancer micrometastases.
隐匿性血行微转移是可手术切除的原发性乳腺癌患者发生转移复发和癌症相关死亡的主要原因。尽管灵敏的免疫细胞化学和分子方法能够检测出骨髓（BM）中单个乳腺癌细胞，而骨髓是转移复发的主要部位，但目前的检测技术无法区分无活力的脱落肿瘤细胞和有意义的转移细胞。为了解决这一问题，我们使用针对p185erbB2癌蛋白的单克隆抗体9G6进行免疫细胞化学双重标记，分析了52例局部区域受限的原发性乳腺癌患者骨髓中细胞角蛋白-18阳性播散性乳腺癌细胞上erbB2过表达的相关性。在52例患者中的31例（60%）检测到骨髓微转移灶上p185erbB2的表达，这与诸如淋巴结受累、原发肿瘤大小、分化程度或原发肿瘤细胞上p185erbB2的表达等既定风险因素无关。经过64个月的中位随访，p185erbB2阳性骨髓微转移患者发生致命性转移复发的频率高于p185erbB2阴性微转移患者（分别为21例和7例事件；P = 0.032）。在多变量分析中，p185erbB2阳性微转移灶的存在是一个独立的预后因素，总生存的风险比为2.78（95%置信区间，1.11 - 6.96）（P = 0.029）。因此，我们得出结论，erbB2过表达是乳腺癌微转移中具有临床相关性的一个亚群的特征。
