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Claudins 在头颈部鳞状细胞癌中的预后作用。

The prognostic role of claudins in head and neck squamous cell carcinomas.

机构信息

Department of Experimental Pharmacology, National Institute of Oncology, Budapest, Hungary.

出版信息

Pathol Oncol Res. 2014 Jan;20(1):99-106. doi: 10.1007/s12253-013-9665-6. Epub 2013 Jul 12.

Abstract

The expression of tight junction proteins is frequently altered in epithelial cancers. The loss of cell-cell adhesion associates with enhanced metastatic potential, which underlies the role of altered expression pattern of tight junction component claudins (CLDNs). Our study assessed the expression of CLDN 1, 2, 3, 4, 7, 8 and 10 in squamous cell carcinoma of the head and neck region (HNSCC) including oropahrynx, larynx, and hypopharynx in comparison to normal epithelial tissue of the same patient. The surgical samples were examined by tissue microarray and immunohistochemistry, the expression was calculated by H-score, which took account of intensity and percentage of positivity as well. Both normal and cancerous tissue proved negative for CLDN 3, 8 and 10. Normal epithelia showed mild expression of CLDN 4, but the minimal positivity disappeared in squamous cancer. In case of CLDN 1 and CLDN 7 we demonstrated significantly increased intensity in cancer, while CLDN 2 showed decreased expression compared with normal epithelium. The normal polarity and distribution of claudins were lost in HNSCC. Moreover, preserved expression of CLDN 2 (but not that of 1 and 7) was associated with better survival, which suggested a potential prognostic role of CLDN 2.

摘要

紧密连接蛋白的表达在上皮性肿瘤中经常发生改变。细胞间黏附的丧失与增强的转移潜能相关,这是紧密连接成分 Claudin(CLDN)表达模式改变的作用基础。我们的研究评估了 CLDN1、2、3、4、7、8 和 10 在头颈部鳞状细胞癌(HNSCC)中的表达,包括口咽、喉和下咽,并与同一患者的正常上皮组织进行了比较。通过组织微阵列和免疫组织化学检查了手术样本,通过 H 评分计算了表达,该评分考虑了强度和阳性百分比。CLDN3、8 和 10 在正常组织和癌组织中均为阴性。正常上皮组织中 CLDN4 的表达较弱,但在鳞状癌细胞中,其最低阳性度消失了。在 CLDN1 和 CLDN7 的情况下,我们证明了癌症中强度显著增加,而与正常上皮组织相比,CLDN2 的表达减少。CLDN 的正常极性和分布在 HNSCC 中丢失。此外,CLDN2 的表达(而非 1 和 7)的保留与更好的生存相关,这表明 CLDN2 具有潜在的预后作用。

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