Assessment of highly angiogenic and disseminated in the peripheral blood disease in breast cancer patients predicts for resistance to adjuvant chemotherapy and early relapse
Assessment of highly angiogenic and disseminated in the peripheral blood disease in breast cancer patients predicts for resistance to adjuvant chemotherapy and early relapse
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DOI：
10.1002/ijc.11593
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发表时间：
2004-02-10
影响因子：
6.4
通讯作者：
Georgoulias, V
中科院分区：
文献类型：
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作者：
Giatromanolaki, A;Koukourakis, MI;Georgoulias, V
肿瘤分子特征的评估与隐匿性恶性细胞的检测相结合，可以提供重要的临床信息，超出了乳腺癌的标准分期。采用巢式RT-PCR技术，我们前瞻性地评估了存在的细胞角蛋白-19（CK 19）mRNA阳性细胞在血液中的100例乳腺癌手术患者开始辅助化疗和局部放疗前。收集组织标本，检测雌激素受体（ER）和前列腺素受体（PgR）、c-erbB-2过表达、mu-p53和bcl-2蛋白积聚、增殖指数和微血管密度（MVD）。33%的患者外周血中检测到CK-19 mRNA阳性细胞。在25%的患者中同时显示高肿瘤内MVD和CK-19 mRNA阳性细胞，其特征是高度血管生成和在外周血（HAD）疾病中播散。CK-19阳性细胞的检测与MVD增加显著相关（p = 0.002）。在单变量分析中（中位随访30个月），CK 19 mRNA检测和MVD是与短期无复发生存期（RFS）相关的最重要因素（p < 0.0001）。在多因素分析中，CK 19阳性、高MVD和c-erbB-2过表达是与复发相关的唯一显著独立变量（p分别为0.0005、0.03和0.04）。HAD患者的预期复发率接近70%，
The assessment of tumor molecular features in combination with the detection of occult malignant cells may provide important clinical information, beyond the standard staging of breast cancer. Using a nested RT-PCR technique, we assessed prospectively the presence of cytokeratin-19 (CK19) mRNA positive cells in the blood of 100 operated patients with breast cancer before the initiation of adjuvant chemotherapy and local radiotherapy. Tissue samples were pro- spectively collected and analyzed for estrogen (ER) and pro- gesterone (PgR) receptor, c-erbB-2 overexpression, mutant-p53 and bcl-2 protein accumulation, proliferation index and microvessel density (MVD). CK-19 mRNA-positive cells were detected in the peripheral blood of 33% of patients. Simultaneous display of high intratumoral MVD and of CK-19 mRNA-positive cells, which characterized highly angiogenic and disseminated in the peripheral blood (HAD) disease was noted in 25% of patients. Detection of CK-19 positive cells was significantly associated with increased MVD (p = 0.002). In univariate analysis (median follow-up 30 months) CK19 mRNA detection and MVD were the most significant factors related to a short relapse-free survival (RFS), (p < 0.0001). In multivariate analysis, CK19 positivity, high MVD and c-erbB-2 overexpression were the only significant and independent variables associated with relapse (p = 0.0005, 0.03 and 0.04, respectively). Patients with HAD had an expected relapse rate close to 70% vs.