Identification of a New Panel of Serum Autoantibodies Associated with the Presence of In situ Carcinoma of the Breast in Younger Women
Identification of a New Panel of Serum Autoantibodies Associated with the Presence of In situ Carcinoma of the Breast in Younger Women
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DOI：
10.1158/1078-0432.ccr-08-3307
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发表时间：
2009-07-15
影响因子：
11.5
通讯作者：
Solassol, Jerome
中科院分区：
文献类型：
--
作者：
Desmetz, Caroline;Bascoul-Mollevi, Caroline;Solassol, Jerome
目的：我们研究了使用一组自身抗体的多个肿瘤相关蛋白作为乳腺癌的早期检测方法的可行性，更具体地说，原位癌（CIS）。实验设计：PPIA，PRDX 2，和FKBP 52被确定为早期乳腺癌自身抗原的蛋白质组学方法。由这三种抗原和两种先前描述的自身抗原HSP 60和MUC 1组成的一组抗体的血清反应性使用特异性ELISA在235个样品（60个来自原发性乳腺癌患者，82个来自CIS患者，93个来自健康对照）上进行测试。FKBP 52，PPIA和PRDX 2的mRNA和蛋白表达水平进行了评估，通过逆转录-PCR和免疫组化在早期乳腺tumors.Results：三个五个自身抗体，FKBP 52，PPIA和PRDX 2，表现出显着增加的反应性，在原发性乳腺癌和CIS与健康对照组相比。当结合使用时，这五种标记物显著区分了原发性乳腺癌[曲线下接受者操作特征面积，0.73; 95%置信区间（95%CI），0.60-0.79]和CIS（曲线下接受者操作特征面积，0.80; 95%CI，0.71-0.85）与健康个体。重要的是，自身抗体组的受试者工作特征曲线下面积值能够区分CIS，包括高级别，与50岁以下女性的健康对照（受试者工作特征曲线下面积，0.85; 95%CI，0.61-0.92）。最后，只有FKBP 52的mRNA和蛋白水平被发现增加在CIS和原发性乳腺癌与健康breast tissue.Conclusions相比：这种自身抗体检测对一个面板的五个抗原允许早期乳腺癌，特别是CIS，和健康个体之间的准确区分。这些结果可能有助于检测早期乳腺癌作为乳房X光检查的辅助手段，特别是在50岁以下患有侵袭性癌症的女性中。
Purpose: We examined the feasibility of using a panel of autoantibodies to multiple tumor-associated proteins as a method for early detection of breast cancer and, more particularly, carcinoma in situ (CIS).Experimental Design: PPIA, PRDX2, and FKBP52 were identified as early-stage breast cancer autoantigens by proteomic approaches. The seroreactivity of a panel of antibodies consisting of these three antigens and two previously described autoantigens, HSP60 and MUC1, was tested on 235 samples (60 from primary breast cancer patients, 82 from CIS patients, and 93 from healthy controls) with the use of specific ELISAs. FKBP52, PPIA, and PRDX2 mRNA and protein expression levels were evaluated by reverse transcription-PCR and immunohistochemistry in early-stage breast tumors.Results: Three of five autoantibodies, FKBP52, PPIA, and PRDX2, showed significantly increased reactivity in primary breast cancer and CIS compared with healthy controls. When combined, the five markers significantly discriminated primary breast cancer [receiver operating characteristic area under the curve, 0.73; 95% confidence interval (95% Cl), 0.60-0.79] and CIS (receiver operating characteristic area under the curve, 0.80; 95% Cl, 0.71-0.85) from healthy individuals. Importantly, the receiver operating characteristic-area under the curve value of the autoantibody panel was able to distinguish CIS, including high grades, from healthy controls in women under the age of 50 years (receiver operating characteristic area under the curve, 0.85; 95% Cl, 0.61-0.92). Finally, only FKBP52 mRNA and protein levels were found to be increased in CIS and primary breast cancer compared with healthy breast tissue.Conclusions: This autoantibody assay against a panel of five antigens allows for an accurate discrimination between early-stage breast cancer, especially CIS, and healthy individuals. These results could be of interest in detecting early breast cancer as an aid to mammography, especially in women under the age of 50 years with aggressive cancers.