Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
PLoS One. 2012;7(2):e30997. doi: 10.1371/journal.pone.0030997. Epub 2012 Feb 17.
Circulating autoantibodies occur more frequently in cancer patients than in patients without cancer.
We examined sera from patients referred for pelvic mass symptoms to a tertiary university clinic. A total of 127 were diagnosed with epithelial ovarian cancer while 386 had a benign condition. A screen for IgG anti-nuclear antibodies (ANA) by indirect immunofluorescence on HEp-2 cells confirmed a highly significant overrepresentation of ANA in the cancer group where 40% had detectable (i.e., a titer ≥160) ANA compared with less than 12% in the benign group. The overrepresentation of ANA in the cancer group persisted (p<0.0001) after matching the age-profile of the benign group with the ovarian cancer group. Only 19 out of 127 patients in the age-matched benign subgroup were positive for ANA corresponding to an 85% specificity at 40% sensitivity of ANA as the only marker for malignancy. No correlation of ANA positivity in either group with specific bands in immunoblots could be demonstrated even though immunoblot positivity was clearly increased in the malignant group (41% vs. 3%). The presence, strength, and type of ANA did not correlate with serum CA-125 values or with staging, and ANA outcome did not contribute with independent diagnostic information. However, survival was significantly shorter in ANA-positive compared with ANA-negative cancer patients and patients with CA-125 below the median CA-125 value in the cancer group had a significantly decreased survival when positive for ANA. ANA status made no difference in the group with CA-125 values above the median. Also, there was a significant correlation between speckled ANA-strength and histological tumor grade.
Circulating antibodies are a promising source for new biomarkers in cancer. Characterization of epitope specificities and measurements of consecutive samples will be important for further elucidating the role of ANA in evaluating ovarian cancer patients.
循环自身抗体在癌症患者中比非癌症患者更常见。
我们检查了因盆腔肿块症状而转介到一所三级大学诊所的患者的血清。共有 127 例被诊断为上皮性卵巢癌，而 386 例为良性疾病。通过在 HEp-2 细胞上进行间接免疫荧光法检测 IgG 抗核抗体（ANA），证实癌症组中 ANA 的高度代表性，其中 40%可检测到（即滴度≥160）ANA，而良性组中不到 12%。在匹配良性组和卵巢癌组的年龄分布后，癌症组中 ANA 的代表性仍然存在（p<0.0001）。在年龄匹配的良性亚组中，只有 19 例患者的 ANA 呈阳性，对应于 ANA 作为唯一恶性标志物的 85%特异性和 40%敏感性。即使在恶性组中免疫印迹阳性明显增加（41%比 3%），也无法证明两组中 ANA 阳性与免疫印迹中的特定条带相关。ANA 阳性与血清 CA-125 值或分期均无相关性，ANA 结果也不能提供独立的诊断信息。然而，ANA 阳性的癌症患者的生存时间明显短于 ANA 阴性的癌症患者，而在癌症组中 CA-125 值低于中位数的患者，如果 ANA 阳性，则生存时间明显缩短。在 CA-125 值高于中位数的组中，ANA 状态没有差异。此外，斑点型 ANA 强度与组织学肿瘤分级之间存在显著相关性。
循环抗体是癌症中新型生物标志物的有前途的来源。对表位特异性的描述和连续样本的测量对于进一步阐明 ANA 在评估卵巢癌患者中的作用将非常重要。
