Correlations between cyclooxygenase-2 expression and angiogenic factors in primary tumors and liver metastases in colorectal cancer
Correlations between cyclooxygenase-2 expression and angiogenic factors in primary tumors and liver metastases in colorectal cancer
复制标题
DOI：
10.1093/jjco/hym080
复制
发表时间：
2007-09-01
影响因子：
2.4
通讯作者：
Sugihara, Kenichi
中科院分区：
文献类型：
--
作者：
Nakamoto, Regina Hiromi;Uetake, Hiroyuki;Sugihara, Kenichi
背景：结直肠癌（CRC）的生长和转移需要血管生成，并且已经鉴定出肿瘤血管生成的几种正调节因子。环加氧酶-2 (COX-2) 已知在多种人类癌症中升高，通过诱导血管生成因子来调节血管生成。本研究的目的是阐明原发性结直肠癌和相应的转移性肝癌配对组织标本中COX-2、血管内皮生长因子A和C、胸苷磷酸化酶（TP）和微血管密度（MVD）的水平并评估其关系。方法：对44例结直肠癌患者的原发性肿瘤和相应的转移性肝癌对的组织样本进行免疫组织化学评估COX-2、VEGF-A、VEGF-C、 TP和MVD。结果：原发性和相应的转移性肝肿瘤往往对COX-2（P = 0.005，rs = 0.428）、VEGF-A（P = 0.039，rs = 0.314）、TP（P = 0.005，rs = 0.422）和MVD（P = 0.046，rs = 0.304) 通过 Spearman 等级检验。肝转移瘤中COX-2免疫反应率高于原发瘤（P = 0.002），原发瘤中VEGF-A免疫反应率高于肝转移瘤（P = 0.0004）。原发性和转移性肝肿瘤之间的 TP 免疫反应性发生率和 MVD 水平没有差异（P = 0.247；P = 0.229）。在转移性肝肿瘤（P = 0.033）和原发性肿瘤（P = 0.008）中发现COX-2免疫反应性和VEGF-A免疫反应性之间存在显着相关性。结论：原发性CRC和肝转移瘤中COX-2、VEGF-A、TP和MVD之间的正相关性将有助于通过分析原发性肿瘤来预测肝转移瘤的血管生成活性，从而允许个体化治疗癌症治疗选择。
Background: Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and several positive regulators of tumor angiogenesis have been identified. Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing angiogenic factors. The aim of this study was to clarify the levels and evaluate the relationships of COX-2, vascular endothelial growth factor A and C, thymidine phosphorylase (TP) and microvascular density (MVD) in paired tissue specimens between primary CRC and corresponding metastatic liver cancer.Methods: Tissue samples from pairs of primary tumors and corresponding metastatic liver tumors from 44 patients with CRC were immunohistochemically evaluated for COX-2, VEGF-A, VEGF-C, TP and MVD.Results: The primary and corresponding metastatic liver tumors tended to show concordant immunoreactivity for COX-2 (P = 0.005, rs = 0.428), VEGF-A (P = 0.039, rs = 0.314), TP (P = 0.005, rs = 0.422) and MVD (P = 0.046, rs = 0.304) by Spearman rank test. The rate of COX-2 immunoreactivity was higher in liver metastases than in primary tumors (P = 0.002), while the rate of VEGF-A was higher in primary tumors than in liver metastases (P = 0.0004). The incidence of TP immunoreactivity and the level of MVD did not differ between primary and metastatic liver tumors (P = 0.247; P = 0.229). Significant correlations were found between COX-2 immunoreactivity and VEGF-A immunoreactivity in metastatic liver tumors (P = 0.033) as well as in primary tumors (P = 0.008).Conclusion: The positive correlations between COX-2, VEGF-A, TP and MVD in primary CRC and liver metastasis as demonstretaed here will help to predict the angiogenic activity of liver metastasis by analyzing primary tumors, allowing for individualized cancer treatment options.