Li Baohua, Shi Haiyan, Wang Fenfen, Hong Die, Lv Weiguo, Xie Xing, Cheng Xiaodong
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
PLoS One. 2016 May 25;11(5):e0155910. doi: 10.1371/journal.pone.0155910. eCollection 2016.
Aberrant expression of classical cadherins has been observed in tumor invasion and metastasis, but its involvement in cervical carcinogenesis and cancer progression is not clear. We investigated E-, P- and N-cadherin expression and its significance in cervical squamous cell carcinoma (SCC) and cervical intraepithelial neoplasia (CIN). This retrospective study enrolled 508 patients admitted to Women's Hospital, School of Medicine, Zhejiang University with cervical lesions between January 2006 and December 2010. Immunochemical staining was performed in 98 samples of normal cervical epithelium (NC), 283 of CIN, and 127 of early-stage SCC. The association of cadherin staining with clinical characteristics and survival of the patients was evaluated by univariate and multivariate analysis. We found gradients of decreasing E-cadherin expression and increasing P-cadherin expression from NC through CIN to SCC. Aberrant E-cadherin and P-cadherin expression were significantly associated with clinical parameters indicating poor prognosis and shorter patient survival. Interestingly, we found very low levels of positive N-cadherin expression in CIN and SCC tissues that were not related to CIN or cancer. Pearson chi-square tests showed that E-cadherin expression in SCC was inversely correlated with P-cadherin expression (E-P switch), and was not correlated with N-cadherin expression. More important, patients with tissues exhibiting an E-P switch in expression had highly aggressive phenotypes and poorer prognosis than those without E-P switch expression. Our findings suggest that E-cadherin and P-cadherin, but not N-cadherin staining, might be useful in diagnosing CIN and for predicting prognosis in patients with early-stage SCC.
经典钙黏蛋白的异常表达已在肿瘤侵袭和转移中被观察到,但其在子宫颈癌发生和癌症进展中的作用尚不清楚。我们研究了E-钙黏蛋白、P-钙黏蛋白和N-钙黏蛋白在宫颈鳞状细胞癌(SCC)和宫颈上皮内瘤变(CIN)中的表达及其意义。这项回顾性研究纳入了2006年1月至2010年12月期间在浙江大学医学院附属妇产科医院因宫颈病变入院的508例患者。对98例正常宫颈上皮(NC)样本、283例CIN样本和127例早期SCC样本进行了免疫化学染色。通过单因素和多因素分析评估钙黏蛋白染色与患者临床特征和生存的相关性。我们发现从NC到CIN再到SCC,E-钙黏蛋白表达逐渐降低,P-钙黏蛋白表达逐渐升高。E-钙黏蛋白和P-钙黏蛋白的异常表达与提示预后不良和患者生存期较短的临床参数显著相关。有趣的是,我们在与CIN或癌症无关的CIN和SCC组织中发现N-钙黏蛋白阳性表达水平非常低。Pearson卡方检验显示,SCC中E-钙黏蛋白表达与P-钙黏蛋白表达呈负相关(E-P转换),与N-钙黏蛋白表达无关。更重要的是,与未发生E-P转换表达的患者相比,组织中出现E-P转换表达的患者具有高度侵袭性的表型和更差的预后。我们的研究结果表明,E-钙黏蛋白和P-钙黏蛋白染色,而非N-钙黏蛋白染色,可能有助于诊断CIN和预测早期SCC患者的预后。