Humoral immune responses to MUC1 in women with a BRCA1 or BRCA2 mutation
Humoral immune responses to MUC1 in women with a BRCA1 or BRCA2 mutation
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DOI：
10.1016/j.ejca.2007.04.007
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发表时间：
2007-07-01
影响因子：
8.4
通讯作者：
von Mensdorff-Pouilly, S.
中科院分区：
文献类型：
--
作者：
Hermsen, B. B. J.;Verheijen, R. H. M.;von Mensdorff-Pouilly, S.
简介：乳腺癌患者的早期疾病和自然的体液反应MUC 1有一个良好的预后，这表明MUC 1抗体（ab）在控制血源性肿瘤的传播和生长的可能作用。本研究的目的是评估遗传性乳腺癌高风险女性对MUC 1的体液免疫应答，以研究这种免疫应答是否可以在疾病预防中发挥作用。材料和方法：CA 15.3（U/mL），IgG和IgM抗体对MUC 1（任意单位/mL，Arb-U/mL）在从422名患有乳腺癌/卵巢癌遗传性高风险的女性中获得的血清样本中进行测量，其中127名BRCA 1/2携带者，参加VU大学医学中心的家族性癌症诊所，并来自370名年龄匹配的健康对照。从患乳腺癌（N = 12）或乳腺癌复发（N = 17）的妇女和接受预防性乳房切除术（N = 12）且无乳腺病变的妇女获得的血清样品也进行了测试。BRCA 1/2突变携带者的MUC 1 IgG抗体水平显著低于对照组（P = 0.003）。MUC 1 IgG水平无显著差异（P = 0.53）发生原发性乳腺癌的女性之间（中位数0.72 Arb-U/ml，范围0.52-2.44 Arb-U/ml）和接受预防性乳房切除术且无乳房病变的女性结论：BRCA 1/2突变携带者血清中抗MUC 1天然IgG抗体水平低于健康对照组。此外，与散发性乳腺癌妇女的既往结果相反，在发生乳腺癌的遗传性高风险妇女中未观察到MUC 1 IgG抗体升高。MUC 1底物的预防性免疫治疗可能是降低BRCA 1/2突变携带者患乳腺癌风险的一种策略，可加强肿瘤免疫监视。(C)2007爱思唯尔有限公司保留所有权利。
Introduction: Breast cancer patients with early disease and a natural humoral response to MUC1 have a favourable prognosis, suggesting a possible role of MUC1 antibodies (ab) in controlling haematogenous tumour dissemination and outgrowth. The aim of the study was to evaluate humoral immune responses to MUC1 in women at hereditary high risk of breast cancer to investigate whether this immune response could play a role in the prevention of disease.Materials and methods: CA15.3 (U/mL), and IgG and IgM ab to MUC1 (arbitrary units per mL, Arb-U/mL) were measured in serum samples obtained from 422 women at hereditary high risk of breast/ovarian cancer, of whom 127 BRCA1/2 carriers, attending the Familial Cancer Clinic of the VU University Medical Centre, and from 370 age-matched healthy controls. Serum samples obtained from women who developed breast cancer (N = 12) or breast cancer recurrence (N = 17), and from women who underwent prophylactic mastectomy (N = 12) and had no breast lesions were also tested.Results: CA15.3 ranked significantly higher in mutation carriers than in controls (P = 0.03). MUC1 IgG ab levels ranked significantly lower in BRCA1/2 mutation carriers than in controls (P = 0.003). MUC1 IgG levels were not significantly different (P = 0.53) between women who developed primary breast cancer (median 0.72 Arb-U/ml, range 0.52-2.44 Arb-U/ml) and women who underwent prophylactic mastectomy and had no breast lesions (median 1.04 Arb-U/ml, range 0.43-2.88 Arb-U/ml).Conclusion: Serum levels of natural IgG ab to MUC1 are lower in BRCA1/2 mutation carriers than in healthy controls. Furthermore, in contrast to previous results in women with sporadic breast cancer, no elevated MUC1 IgG ab were seen in women at hereditary high risk who developed breast cancer. Prophylactic immunotherapy with MUC1 substrates may be a strategy to reduce the risk of breast cancer in BRCA1/2 mutation carriers, strengthening tumour immune surveillance. (C) 2007 Elsevier Ltd. All rights reserved.