Department of Pathology, Chang Gung Memorial Hospital, Linko, Chang Gung University, College of Medicine, Taoyuan 333, Taiwan.
Hum Pathol. 2010 Jul;41(7):944-50. doi: 10.1016/j.humpath.2010.01.005. Epub 2010 Mar 23.
Claudins are major tight junction proteins that regulate the integrity and function of tight junctions. Aberrant expression of claudins has been shown in various carcinomas with diverse prognostic implications. However, their expression pattern and prognostic value have not been investigated in nasopharyngeal carcinoma. This is the first study to characterize the expression pattern of claudins 1, 4, and 7 in a cohort of 176 patients with nasopharyngeal carcinoma and a minimum follow-up of 9.4 years. Immunohistochemistry with semiquantitative assessment of expression of claudins 1, 4, and 7 was performed on 176 biopsy specimens. Results were correlated with sex, age, extent of tumor, lymph node status, the presence or absence of distant metastasis, and patient survival. High expression of claudins 1 and 4 (72.2% and 88.1%) and low expression of claudin 7 (82.4%) were frequently detected. Low claudin 4 expression (P = .020) and high claudin 7 expression (P < .001) were associated with distant metastasis. Elevated claudin 7 expression also correlated with high tumor stage (P = .001). Furthermore, decreased claudin 4 expression (P = .003) and increased claudin 7 expression (P < .001) independently predicted shorter distant metastasis-free survival by Cox regression analysis. Claudin 4 and claudin 7 may be a novel biomarker for the prediction of distant metastasis and unfavorable prognosis in nasopharyngeal carcinoma.
紧密连接蛋白家族（Claudins）是构成紧密连接的主要蛋白，其调节着紧密连接的完整性和功能。Claudins 在多种癌症中呈现异常表达，且与不同的预后相关。然而，Claudins 在鼻咽癌中的表达模式和预后价值尚未被研究。本研究首次对 176 例鼻咽癌患者的 Claudin 1、4 和 7 的表达模式进行了特征分析，随访时间至少 9.4 年。采用免疫组化方法对 Claudin 1、4 和 7 的表达进行半定量评估，并分析其与性别、年龄、肿瘤范围、淋巴结状态、有无远处转移以及患者生存的相关性。结果发现 Claudin 1 和 4 （72.2%和 88.1%）高表达，Claudin 7 低表达（82.4%）。Claudin 4 低表达（P =.020）和 Claudin 7 高表达（P <.001）与远处转移相关。Claudin 7 高表达还与肿瘤分期较高相关（P =.001）。此外，Cox 回归分析表明 Claudin 4 低表达（P =.003）和 Claudin 7 高表达（P <.001）独立预测远处无转移生存率降低。Claudin 4 和 Claudin 7 可能是预测鼻咽癌远处转移和不良预后的新型生物标志物。
