Chow L W C, Loo W T Y, Wai C C Y, Lui E L H, Zhu L, Toi M
Hung Chao Hong Integrated Center for Breast Diseases, Department of Surgery, The University of Hong Kong Medical Center, Queen Mary Hospital, Pokfulam, China.
Biomed Pharmacother. 2005 Oct;59 Suppl 2:S298-301. doi: 10.1016/s0753-3322(05)80050-2.
Cyclooxygenase-2 (COX-2) affects cell proliferation, apoptosis, and metastasis of breast cancer, and may also be involved in tumor angiogenesis through vascular endothelial growth factor. Ki67 and p53 are common markers of proliferation and apoptosis in tumor cells. This study investigated the change in expression of COX-2, Ki67, and p53 in solid tumors after the administration of chemotherapeutic drugs.
Fifty patients were eligible to be treated with preoperative 5-fluorouracil, epirubicin, and cyclophosphamide, with celecoxib (FECC). Tumor tissue samples from 10 patients who, diagnosed with invasive ductal carcinoma, completed chemotherapy were examined immunohistochemically for COX-2, Ki67, and p53.
From the 60% of patients who expressed COX-2 and 90% who expressed Ki67 and p53 before treatment, 90% of patients revealed a lower intensity staining for each marker after FECC treatment. However, changes in expression of the three markers did not significantly correlate with tumor size, grade, axillary lymph node status. Immunostained slides clearly showed that the diaminobenzidine intensity was markedly reduced after the three-cycle FECC treatment, which implied the combined regimens be effective to the cancer patients.
This study demonstrates a novel relationship between COX-2, Ki67, and p53 expression of human breast invasive ductal carcinomas. This functional relationship provides support for a potential therapeutic role of COX-2 inhibitors in human breast cancer.
环氧合酶 -2（COX-2）影响乳腺癌细胞的增殖、凋亡和转移，还可能通过血管内皮生长因子参与肿瘤血管生成。Ki67和p53是肿瘤细胞增殖和凋亡的常用标志物。本研究调查了化疗药物给药后实体瘤中COX-2、Ki67和p53表达的变化。
50例患者符合接受术前5-氟尿嘧啶、表柔比星和环磷酰胺联合塞来昔布（FECC）治疗的条件。对10例诊断为浸润性导管癌并完成化疗的患者的肿瘤组织样本进行COX-2、Ki67和p53的免疫组织化学检查。
治疗前60%表达COX-2、90%表达Ki67和p53的患者中，90%的患者在FECC治疗后每种标志物的染色强度降低。然而，这三种标志物表达的变化与肿瘤大小、分级、腋窝淋巴结状态无显著相关性。免疫染色切片清楚显示，三周期FECC治疗后二氨基联苯胺强度明显降低，这表明联合治疗方案对癌症患者有效。
本研究揭示了人乳腺浸润性导管癌中COX-2、Ki67和p53表达之间的新关系。这种功能关系为COX-2抑制剂在人类乳腺癌中的潜在治疗作用提供了支持。
