Laboratory Interdisciplinary of Medical Research, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
PLoS One. 2012;7(4):e32936. doi: 10.1371/journal.pone.0032936. Epub 2012 Apr 6.
Minichromosome maintenance proteins (MCM) are highly expressed in actively replicating cells. The need for biological markers for cervical carcinoma and its precursor lesions is emerging. Our main aim was to determine the immunohistochemical expression of MCM-2 in HIV-positive and -negative dysplastic cervical specimens.
Immunohistochemical analysis of MCM-2 was performed in a total of 352 cervical TMA specimens of normal control, low-grade CIN, high-grade CIN and invasive tumor. 38 specimens were from HIV-positive women. A receiver operating characteristic (ROC) curve was constructed to determine the best cutoff to diagnose high-grade CIN and invasive cervical cancer.
In the progression from normal epithelium to high-grade CIN and invasive tumor we found significant differences in the MCM-2 expression (p<0.05). Based on the ROC curve of 80% with an area under the curve (AUC) of 0.78, expression of MCM-2 to diagnose high-grade CIN and invasive tumor resulted in sensitivity of 81%, specificity of 66%, a positive predictive value (PPV) of 86% and a negative predictive value (NPV) of 57%. HIV-positive cervices revealed a decreasing expression of MCM-2 in both LGCIN and HGCIN compared with HIV-negative specimens (p<0.0001).
The present study suggests that immunohistochemical MCM-2 may not be a promising biomarker for diagnosing high-grade CIN and invasive cancer.
微小染色体维持蛋白（MCM）在活跃复制的细胞中高度表达。对于宫颈癌及其前体病变的生物标志物的需求正在出现。我们的主要目的是确定 MCM-2 在 HIV 阳性和阴性的宫颈异型标本中的免疫组织化学表达。
对总共 352 例正常对照、低级别 CIN、高级别 CIN 和浸润性肿瘤的宫颈 TMA 标本进行 MCM-2 的免疫组织化学分析。38 例标本来自 HIV 阳性妇女。构建受试者工作特征（ROC）曲线以确定诊断高级别 CIN 和浸润性宫颈癌的最佳截断值。
从正常上皮到高级别 CIN 和浸润性肿瘤的进展中，我们发现 MCM-2 表达存在显著差异（p<0.05）。基于 ROC 曲线，80%的曲线下面积（AUC）为 0.78，MCM-2 表达诊断高级别 CIN 和浸润性肿瘤的敏感性为 81%，特异性为 66%，阳性预测值（PPV）为 86%，阴性预测值（NPV）为 57%。与 HIV 阴性标本相比，HIV 阳性宫颈在低级别 CIN 和高级别 CIN 中均显示出 MCM-2 表达降低（p<0.0001）。
本研究表明，免疫组织化学 MCM-2 可能不是诊断高级别 CIN 和浸润性癌症的有前途的生物标志物。
