Chatterjee Madhumita, Hurley Laura C, Tainsky Michael A
Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, United States.
Cancer Biology Graduate Program, Wayne State University School of Medicine, Detroit, MI 48201, United States.
Gynecol Oncol Rep. 2017 Jun 15;21:37-44. doi: 10.1016/j.gore.2017.06.006. eCollection 2017 Aug.
Paraneoplastic syndromes are a group of rare disorders that can be triggered by an abnormal immune response to proteins from tumors of the lung, ovary, lymphatics, or breast. Paraneoplastic clinical syndromes affect < 1% of patients with cancer; however, the frequency of subclinical levels of paraneoplastic autoantibodies in asymptomatic patients with cancer is unknown. Numerous studies have reported that ovarian cancer patients show signs of paraneoplastic neurological syndromes (PNSs) before or after their cancers are diagnosed. PNSs arise from a tumor-elicited immune response against onconeural antigens that are shared by tissues of nervous system, muscle, and tumor cells. Studies on the serum IgGs obtained from ovarian cancer patients have indicated the presence of onconeural antibodies in the absence of any PNS symptoms. The occurrence of PNSs is low in ovarian cancer patients and it can be accompanied by onconeural antibodies. The diagnosis of PNSs is accompanied by a suspicion of a malignant tumor such that neurologists typically refer such patients for a tumor diagnostic workup. There will be tremendous utility if subclinical levels (without paraneoplastic neurological symptoms or myositis) of these autoantibodies to paraneoplastic antigens can be exploited to screen asymptomatic high-risk patients for ovarian cancer, and used as biomarkers in immunoassays for the early detection or recurrence of ovarian cancer. Ovarian cancer overall survival is likely to be improved with early detection. Therefore, a panel of onconeural antigens that can detect paraneoplastic autoantibodies in patient sera should provide diagnostic utility for an earlier therapeutic intervention. Here we review the usefulness of PNS and other paraneoplastic syndromes and their association with paraneoplastic antigens to exploit these autoantibody biomarkers to form diagnostic multi-analyte panels for early detection of ovarian cancer.
副肿瘤综合征是一组罕见的疾病，可由对来自肺、卵巢、淋巴管或乳腺肿瘤的蛋白质的异常免疫反应引发。副肿瘤临床综合征影响不到1%的癌症患者；然而，无症状癌症患者中副肿瘤自身抗体亚临床水平的频率尚不清楚。许多研究报告称，卵巢癌患者在癌症诊断之前或之后会出现副肿瘤神经综合征（PNSs）的症状。PNSs源于肿瘤引发的针对肿瘤神经抗原的免疫反应，这些抗原为神经系统、肌肉和肿瘤细胞的组织所共有。对卵巢癌患者血清IgG的研究表明，在没有任何PNS症状的情况下存在肿瘤神经抗体。PNSs在卵巢癌患者中的发生率较低，并且可能伴有肿瘤神经抗体。PNSs的诊断伴随着对恶性肿瘤的怀疑，因此神经科医生通常会将此类患者转诊进行肿瘤诊断检查。如果这些针对副肿瘤抗原的自身抗体的亚临床水平（无副肿瘤神经症状或肌炎）能够用于筛查无症状的卵巢癌高危患者，并用作免疫测定中卵巢癌早期检测或复发的生物标志物，将会有巨大的实用价值。早期检测可能会提高卵巢癌的总体生存率。因此，一组能够检测患者血清中副肿瘤自身抗体的肿瘤神经抗原应该为更早的治疗干预提供诊断效用。在这里，我们综述PNS和其他副肿瘤综合征的有用性，以及它们与副肿瘤抗原的关联，以利用这些自身抗体生物标志物形成用于卵巢癌早期检测的诊断多分析物检测板。
