宫颈细胞学中 Ezrin 和 E-cadherin 的表达谱：宫颈癌肿瘤进展的预后标志物。
Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer.
机构信息
Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lazaro Cardenas s/n, Ciudad Universitaria, CP, 39090, Chilpancingo, Guerrero, Mexico.
Laboratorio de Biología Celular del Cáncer, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico.
出版信息
BMC Cancer. 2018 Mar 27;18(1):349. doi: 10.1186/s12885-018-4243-7.
BACKGROUND
Cervical cancer (CC) is the fourth cause of mortality by neoplasia in women worldwide. The use of immunomarkers is an alternative tool to complement currently used algorithms for detection of cancer, and to improve selection of therapeutic schemes. Aberrant expression of Ezrin and E-cadherin play an important role in tumor invasion. In this study we analyzed Ezrin and E-cadherin expression in liquid-based cervical cytology samples, and evaluated their potential use as prognostic immunomarkers.
METHODS
Immunocytochemical staining of Ezrin and E-cadherin was performed in cervical samples of 125 patients. The cytological or histological diagnostic was performed by Papanicolaou staining or H&E staining, respectively. HPV genotyping was determined using INNO-LIPA Genotyping Extra kit and the HPV physical status by in situ hybridization. Ezrin expression in HaCaT, HeLa and SiHa cell lines was determined by immunocytochemistry, immunofluorescence and Western blot.
RESULTS
High Ezrin expression was observed in cervical cancer samples (70%), samples with multiple infection by HR-HPV (43%), and samples with integrated viral genome (47%). High Ezrin expression was associated with degree of SIL, viral genotype and physical status. In contrast, low E-cadherin expression was found in cervical cancer samples (95%), samples with multiple infection by HR-HPV/LR-HPV (87%) and integrated viral genome (72%). Low E-cadherin expression was associated with degree of SIL and viral genotype. Interestingly, Ezrin nuclear staining was associated with degree of SIL and viral genotype. High Ezrin expression, high percent of nuclear Ezrin and low E-cadherin expression behaved as risk factors for progression to HSIL and cervical cancer.
CONCLUSIONS
Ezrin and E-cadherin expression profile in cervical cytology samples could be a potential prognostic marker, useful for identifying cervical lesions with a high-risk of progression to cervical cancer.
背景
宫颈癌（CC）是全球女性因肿瘤导致死亡的第四大原因。免疫标志物的使用是一种补充目前用于癌症检测的算法的替代工具，可提高治疗方案的选择。Ezrin 和 E-cadherin 的异常表达在肿瘤侵袭中发挥重要作用。在这项研究中，我们分析了液基宫颈细胞学样本中的 Ezrin 和 E-cadherin 表达，并评估了它们作为预后免疫标志物的潜在用途。
方法
对 125 例患者的宫颈样本进行 Ezrin 和 E-cadherin 的免疫细胞化学染色。细胞学或组织学诊断分别通过巴氏染色或 H&E 染色进行。使用 INNO-LIPA Genotyping Extra 试剂盒进行 HPV 基因分型，原位杂交法确定 HPV 物理状态。通过免疫细胞化学、免疫荧光和 Western blot 确定 HaCaT、HeLa 和 SiHa 细胞系中 Ezrin 的表达。
结果
在宫颈癌样本（70%）、HPV 高风险型（HR-HPV）多重感染样本（43%）和整合病毒基因组样本（47%）中观察到高 Ezrin 表达。高 Ezrin 表达与 SIL 程度、病毒基因型和物理状态有关。相反，在宫颈癌样本（95%）、HPV 高风险型/低风险型（HR-HPV/LR-HPV）多重感染样本（87%）和整合病毒基因组样本（72%）中发现低 E-cadherin 表达。低 E-cadherin 表达与 SIL 程度和病毒基因型有关。有趣的是，Ezrin 核染色与 SIL 程度和病毒基因型有关。高 Ezrin 表达、高核 Ezrin 百分比和低 E-cadherin 表达是向 HSIL 和宫颈癌进展的危险因素。
结论
宫颈细胞学样本中 Ezrin 和 E-cadherin 的表达谱可能是一种潜在的预后标志物，可用于识别具有向宫颈癌进展高风险的宫颈病变。
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