Scholl S M, Lidereau R, de la Rochefordière A, Le-Nir C C, Mosseri V, Noguès C, Pouillart P, Stanley F R
Départment de Médecine Oncologique, Institut Curie, Paris, France.
Breast Cancer Res Treat. 1996;39(3):275-83. doi: 10.1007/BF01806155.
Earlier results [1], suggesting an autocrine tumor cell stimulation by CSF-1, are in agreement with data by Fildermann et al. [2], showing an enhanced motility and invasiveness in the CSF-1 receptor expressing BT20 breast cancer cell line upon stimulation with recombinant CSF-1. Tumor-cell secreted CSF-1 has also been shown to cause monocyte recruitment, but not cytotoxicity [3]. Down-regulation of monocyte class II antigen expression after exposure to high concentrations of CSF-1 [4] may decrease macrophage-mediated tumor cytotoxicity and favor tolerance. Raised CSF-1 serum levels may thus increase tumor metastatic behavior as well as cause immune suppression in advanced stage disease. We set out to evaluate serum CSF-1 levels in primary and metastatic breast cancer. Serum samples from one hundred and eighteen primary breast cancer patients and seventy-five patients with metastatic disease were assayed by radio-immuno-assay (RIA) for circulating colony-stimulating factor 1. Mean serum levels were significantly higher in the metastatic population (9.7 ng/ml +/- 0.8) as compared to the patients with primary tumors (4.2 +/- 0.2) (p = 0.0001). Patients with early stage tumors (T0/T1/T2) had significantly lower levels than patients with tumors of larger size (T3/T4) (p = 0.0001). Relapse and survival statistics were analyzed using Kaplan-Meier estimates. Samples from 118 primary breast cancer patients were available to study. The median follow up was 85 months (range: 1-108). An elevated CSF-1 concentration (> 6.6 ng/ml or > 550 Units/ml) was associated with a shorter disease free interval (p = 0.03). In a multivariate analysis, including T (clinical tumor size), N (clinical node status), histological grade, and hormone receptor status, CSF-1 remained significantly associated with a poorer outcome (relative risk of relapse: RR: 3.3 [1.3-8.5]), together with tumor size (RR: 2.8[1-8.2]) and clinically involved nodes (RR: 4.1[2.1-8]). These results were not modified following adjustment for type of treatment. We conclude that raised circulating CSF-1 levels may be an indicator of early metastatic relapse.
早期结果[1]表明CSF-1对肿瘤细胞有自分泌刺激作用，这与菲尔德曼等人[2]的数据一致，他们的数据显示，在用重组CSF-1刺激后，表达CSF-1受体的BT20乳腺癌细胞系的运动性和侵袭性增强。肿瘤细胞分泌的CSF-1也已被证明可引起单核细胞募集，但无细胞毒性[3]。暴露于高浓度CSF-1后单核细胞II类抗原表达下调[4]可能会降低巨噬细胞介导的肿瘤细胞毒性并有利于免疫耐受。因此，血清CSF-1水平升高可能会增加肿瘤转移行为，并在晚期疾病中引起免疫抑制。我们着手评估原发性和转移性乳腺癌患者的血清CSF-1水平。采用放射免疫分析法（RIA）检测了118例原发性乳腺癌患者和75例转移性疾病患者的血清样本中的循环集落刺激因子1。转移性疾病患者的平均血清水平（9.7 ng/ml±0.8）显著高于原发性肿瘤患者（4.2±0.2）（p = 0.0001）。早期肿瘤（T0/T1/T2）患者的水平显著低于肿瘤体积较大（T3/T4）的患者（p = 0.0001）。使用Kaplan-Meier估计法分析复发和生存统计数据。有118例原发性乳腺癌患者的样本可供研究。中位随访时间为85个月（范围：1 - 108个月）。CSF-1浓度升高（> 6.6 ng/ml或> 550单位/ml）与无病间期缩短相关（p = 0.03）。在一项多变量分析中，包括T（临床肿瘤大小）、N（临床淋巴结状态）、组织学分级和激素受体状态，CSF-1仍然与较差的预后显著相关（复发相对风险：RR：3.3 [1.3 - 8.5]），同时还有肿瘤大小（RR：2.8 [1 - 8.2]）和临床受累淋巴结（RR：4.1 [2.1 - 8]）。在对治疗类型进行调整后，这些结果并未改变。我们得出结论，循环CSF-1水平升高可能是早期转移性复发的一个指标。
