von Mensdorff-Pouilly S, Verstraeten A A, Kenemans P, Snijdewint F G, Kok A, Van Kamp G J, Paul M A, Van Diest P J, Meijer S, Hilgers J
Departments of Obstetrics and Gynecology, Clinical Chemistry, Pathology, and Surgery, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
J Clin Oncol. 2000 Feb;18(3):574-83. doi: 10.1200/JCO.2000.18.3.574.
Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease.
We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population.
A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P =.0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P =.0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P =.026).
Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influence the outcome of disease.
多形性上皮粘蛋白（PEM或MUC1）正作为腺癌患者免疫治疗的疫苗底物进行研究。本研究分析了早期乳腺癌患者中自然产生的MUC1抗体的发生率，并将预处理血清中这些抗体的存在与疾病转归相关联。
我们采用酶联免疫分析法（PEM.CIg）检测了154例乳腺癌患者（52例I期疾病患者和102例II期疾病患者）及302例对照的预处理血清样本中针对MUC1的免疫球蛋白G（IgG）和免疫球蛋白M（IgM）抗体，该方法使用与牛血清白蛋白偶联的MUC1三串联重复肽。乳腺癌患者的疾病特异性生存时间中位数为74个月（范围15至118个月）。阳性检测结果定义为MUC1 IgG或IgM抗体水平等于或高于在整个乳腺癌人群中获得的相应四舍五入后的中位数结果。
预处理血清中MUC1 IgG和IgM抗体的阳性检测结果与I期和II期（P = 0.0116）乳腺癌患者的疾病特异性生存显著获益相关。在多变量分析中，阳性IgG和IgM MUC1抗体水平对分期（P = 0.0437）具有显著的额外预后价值。无病生存概率无显著差异。然而，MUC1 IgG和IgM抗体检测呈阳性且复发的II期患者主要为局部复发或对侧疾病，而体液反应阴性的患者则主要为远处复发（P = 0.026）。
对MUC1有自然体液反应性的早期乳腺癌患者远处无复发的概率更高，疾病特异性生存更好。MUC1抗体可能通过协助破坏循环或种植的表达MUC1的肿瘤细胞来控制血源性肿瘤的播散和生长。在辅助治疗中用MUC1衍生的（糖）肽对乳腺癌患者进行疫苗接种可能会对疾病转归产生有利影响。
