The effect of cyclooxygenase-2 expression on tumor vascularity in advanced stage ovarian serous carcinoma
The effect of cyclooxygenase-2 expression on tumor vascularity in advanced stage ovarian serous carcinoma
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DOI：
10.1002/cncr.11650
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发表时间：
2003-10-01
期刊：
影响因子：
6.2
通讯作者：
Munkarah, AR
中科院分区：
文献类型：
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作者：
Ali-Fehmi, R;Che, MX;Munkarah, AR
背景环氧合酶-2（考克斯-2）似乎参与了恶性转化和肿瘤进展过程中的各个步骤。研究表明考克斯-2过表达与增殖增加、凋亡减少和血管生成相关。通过免疫组织化学方法评估了125例高级别、晚期（III-IV期）浆液性卵巢癌患者的标本的考克斯-2、p53、bcl-2、表皮生长因子受体（EGFR）和Her-2/neu表达以及CD 34染色的微血管密度（MVD）。统计分析考克斯-2表达与临床病理特征、肿瘤微血管密度及其他分子标志物表达的相关性。考克斯-2表达对生存的影响通过生存分析来确定。考克斯-2的表达与肿瘤MVD显著相关（斯皮尔曼等级相关检验：r = 0.41; P < 0.001）。考克斯-2表达与EGFR、Her-2/ neu、bcl-2或p53表达水平之间未观察到相关性。与肿瘤低表达患者相比，肿瘤高表达考克斯-2患者的预后更差（死亡风险比，2.0; 95%可信区间，1.2-3.5; P < 0.001）。多因素分析显示，在分析的不同预后因素中，考克斯-2表达是生存率的最强预测因子。目前的研究表明，考克斯-2表达与高级别、高分期浆液性卵巢癌患者的生存率显著相关。考克斯-2的表达也与肿瘤血管生成相关，但与EGFR、Her-2/neu或p53表达无关。除了它们的预后意义，更好地了解这些分子变化的生物学可能有助于确定卵巢癌患者治疗的新靶点。Cancer 2003;98：1423-9. (C)2003年美国癌症协会。
BACKGROUND. Cyclooxygenase-2 (COX-2) seems to be involved at various steps in the processes of malignant transformation and tumor progression. Investigations have shown that COX-2 overexpression is associated with increased proliferation, reduced apoptosis, and angiogenesis.METHODS. Specimens from 125 patients with high-grade, advanced-stage (Stage III-IV) serous ovarian carcinoma were evaluated by immunohistochemistry for COX-2, p53, bcl-2, epidermal growth factor receptor (EGFR), and Her-2/neu expression and for CD34-stained microvessel density (MVD). Statistical analysis was performed to investigate the correlations between COX-2 expression and 1) clinicopathologic characteristics, 2) tumor MVD, and 3) expression of other molecular markers. The effect of COX-2 expression on survival was determined using survival analysis.RESULTS. increased COX-2 expression was significantly correlated with tumor MVD (Spearman rank correlation test: r = 0.41; P < 0.001). There was no association observed between COX-2 expression and expression levels of EGFR, Her-2/ neu, bcl-2, or p53. Patients who had tumors that showed high COX-2 expression had a worse prognosis compared with patients who had tumors with low expression (death hazard ratio, 2.0; 95% confidence interval, 1.2-3.5; P < 0.001). A multivariate analysis revealed that COX-2 expression was the strongest predictor of survival among the different prognostic factors analyzed.CONCLUSIONS. The current study demonstrated that COX-2 expression was correlated significantly with survival in patients with high-grade, high-stage serous ovarian carcinoma. Expression of COX-2 also was correlated with tumor angiogenesis but not with EGFR, Her-2/neu, or p53 expression. In addition to their prognostic significance, a better understanding of the biology of these molecular changes may help identify new targets for therapy in patients with ovarian carcinoma. Cancer 2003;98:1423-9. (C) 2003 American Cancer Society.