Prognostic impact of cyclooxygenase-2 in breast cancer.
Prognostic impact of cyclooxygenase-2 in breast cancer.
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DOI：
10.3816/cbc.2004.n.006
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发表时间：
2004-02-01
影响因子：
3.1
通讯作者：
Hauptmann, Steffen
中科院分区：
文献类型：
--
作者：
Denkert, Carsten;Winzer, Klaus-Jurgen;Hauptmann, Steffen
环氧化酶(COX)-2是环氧化酶的诱导异构体，在炎症过程中调节前列腺素的快速生成。环氧合酶-2在多种恶性肿瘤中过表达。本文综述了COX-2在乳腺癌发生发展中的流行病学和临床前数据，并将重点介绍COX-2在乳腺癌预后中的作用的最新研究。在啮齿类动物肿瘤模型中，已经表明用COX-1或COX-2抑制剂治疗可以降低乳腺癌的发病率和生长。可能的机制包括COX-2调节侵袭、增加增殖和抑制凋亡。此外，前列腺素可能有间接作用，例如在肿瘤宿主的相互作用中，如诱导基质芳香化酶活性或增强肿瘤组织中的血管生成。至少有8项不同的免疫组织化学研究调查了COX-2在总共2392例原发性乳腺癌中的表达，其中40%发现COX-2阳性。COX-2过表达与淋巴结转移、分化差、肿瘤大小大等预后不良指标相关。四项研究发现COX-2的过度表达与乳腺癌预后不良有关。这些研究为进一步评价COX抑制剂治疗乳腺癌的可能疗效提供了基础。
Cyclooxygenase (COX)-2, an inducible isoform of cyclooxygenases, regulates the rapid production of high levels of prostaglandins during inflammation. Cyclooxygenase-2 is overexpressed in a variety of malignant tumors. This review discusses epidemiologic and preclinical data on the role of COX-2 in the development and progression of breast cancer, and it will focus on recent studies that investigate the prognostic role of COX-2 in breast cancer. In rodent tumor models it has been shown that treatment with COX-1 or COX-2 inhibitors reduces incidence and growth of breast carcinomas. Possible mechanisms include regulation of invasion, increased proliferation, and suppression of apoptosis by COX-2. Moreover, there may be an indirect effect of prostaglandins, for example in tumor host interactions such as induction of stromal aromatase activity or enhancement of angiogenesis in tumor tissue. At least 8 different immunohistochemical studies have investigated expression of COX-2 in a total of 2392 primary breast carcinomas, of which 40% were found to be COX-2 positive. Overexpression of COX-2 is associated with indicators of poor prognosis, such as lymph node metastasis, poor differentiation, and large tumor size. Four studies have found that overexpression of COX-2 is linked to poor prognosis in breast cancer. These investigations provide the basis for further evaluation of a possible therapeutic effect of COX inhibitors in therapy of breast cancer.