COX-2 expression in dysplasia of the head and neck - Correlation with elF4E
COX-2 expression in dysplasia of the head and neck - Correlation with elF4E
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DOI：
10.1002/1097-0142(20011001)92:7
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发表时间：
2001-10-01
期刊：
影响因子：
6.2
通讯作者：
Glass, J
中科院分区：
文献类型：
--
作者：
Nathan, CAO;Leskov, IL;Glass, J
背景考克斯-2抑制剂在上皮肿瘤的化学预防中显示出前景。eIF 4 E是一种生物标志物，可识别头颈部鳞状细胞癌（HNSCC）确定性治疗后复发的高风险个体。因此，作者希望确定考克斯-2是否在头颈部发育不良中表达，并研究考克斯-2表达与eIF 4 E的相关性，作为确定对考克斯-2应答的潜在替代终点。作者采用免疫组织化学方法研究了考克斯-2和eIF 4 E在正常上皮（n = 8）、不典型增生（n = 51）、肿瘤旁粘膜（n = 11）和头颈癌（n = 19）中的表达。此外，对上述患者样品和HNSCC细胞系的子集进行蛋白质印迹分析。免疫组化显示考克斯-2和eIF 4 E在所有癌组织中表达，而在正常组织中不表达。在异型增生上皮中，eIF 4 E和考克斯-2的表达在所有异型增生组中均显著相关（卡方= 40.3，P < 0.001）。Cochran-Armitage趋势检验显示，表达两种分子标志物的病例比例随着异型增生级别的增加而显著增加（P = 0.001）。Western blot分析显示考克斯-2和eIF 4 E在肿瘤中的表达较癌旁粘膜高。分析的所有三种HNSCC细胞系具有增加的eIF 4 E表达。尽管只有2例考克斯-2表达增加。考克斯-2在不典型增生中的表达提示考克斯-2抑制剂可能在头颈部癌的化学预防中发挥作用，并且考克斯-2与eIF 4 E的相关性提示eIF 4 E可以作为化学预防试验中的潜在替代标记物。(C)2001年美国癌症协会。
BACKGROUND. COX-2 inhibitors have shown promise in chemoprevention of epithelial tumors. eIF4E is a biomarker that has identified individuals at high risk for relapse after definitive treatment for head and neck squamous cell cancer (HNSCC). Hence, the authors wanted to determine if COX-2 is expressed in dysplasia of the head and neck and to study the correlation of expression of COX-2 with eIF4E as a potential surrogate endpoint for determining response to COX-2 inhibitors.METHODS. The authors studied the expression of COX-2 and eIF4E in normal epithelium (n = 8), dysplasia (n = 51), mucosa adjacent to tumors (n = 11), and cancer of the head and neck (n = 19) using immunohistochemistry. In addition, Western blot analysis was performed on a subset of the above patient samples and HNSCC cell lines.RESULTS. Immunohistochemical analysis showed expression of COX-2 and eIF4E in all cancers and no expression in normal tissues. In dysplastic epithelium, there was a significant correlation between the expression of eIF4E and COX-2 for all groups of dysplasia combined (chi-square = 40.3, P < 0.001). A Cochran-Armitage trend test showed a significant increase in the proportion of cases that expressed both molecular markers with increasing grades of dysplasia (P = 0.001). Western blot analysis showed increased expression of COX-2 and eIF4E in tumors compared with adjacent mucosa. All three HNSCC cell lines analyzed had increased expression of eIF4E. although only two had increased COX-2 expression.CONCLUSIONS. Expression of COX-2 in dysplasia suggested that COX-2 inhibitors may play a role in chemoprevention of head and neck cancers and that the correlation of Cox-2 with eIF4E indicates that eIF4E can be a potential surrogate marker in chemoprevention trials. (C) 2001 American Cancer Society.