Fujiwaki Ritsuto, Iida Kohji, Kanasaki Haruhiko, Ozaki Tomoya, Hata Kohkichi, Miyazaki Kohji
Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan.
Hum Pathol. 2002 Feb;33(2):213-9. doi: 10.1053/hupa.2002.31292.
Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing production of angiogenic factors. These mechanisms require clarification in endometrial cancer. COX-2 expression was examined by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) in endometrial cancer, endometrial hyperplasia, and normal endometrium in various phases. We investigated the relationship between COX-2 expression and clinicopathologic variables, microvessel count, and expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). Immunohistochemistry demonstrated COX-2 protein in cancerous epithelial cells but not in stromal cells. COX-2 expression in epithelial cells was significantly greater in endometrial cancer (n = 63) and endometrial hyperplasia (n = 6) than in normal endometrium in any phase (n = 53). Although COX-2 did not correlate with any conventional clinicopathologic factor in patients with endometrial cancer, COX-2 expression was associated with high microvessel count, VEGF expression, and TP expression. By combined analysis of COX-2, VEGF, and TP, tumors with high expression of at least one factor had a significantly higher microvessel count than tumors expressing little of the three factors. We confirmed upregulation of COX-2 mRNA expression by RT-PCR in endometrial cancer (n = 17) compared to normal endometrium (n = 12). COX-2 mRNA expression significantly correlated with VEGF mRNA expression in these tumors. COX-2 is upregulated in endometrial cancer and facilitates tumor growth via angiogenesis produced in associated with VEGF and TP. Specific inhibition of COX-2 may be a useful therapeutic intervention in endometrial cancer.
环氧化酶-2（COX-2）在多种人类癌症中表达升高，它通过诱导血管生成因子的产生来调节血管生成。这些机制在子宫内膜癌中尚需阐明。我们采用免疫组织化学和逆转录聚合酶链反应（RT-PCR）检测了不同时期子宫内膜癌、子宫内膜增生及正常子宫内膜中COX-2的表达情况。我们研究了COX-2表达与临床病理变量、微血管计数以及血管内皮生长因子（VEGF）和胸苷磷酸化酶（TP）表达之间的关系。免疫组织化学显示癌上皮细胞中有COX-2蛋白表达，而基质细胞中无表达。在子宫内膜癌（n = 63）和子宫内膜增生（n = 6）中，上皮细胞中的COX-2表达明显高于任何时期的正常子宫内膜（n = 53）。虽然COX-2与子宫内膜癌患者的任何传统临床病理因素均无相关性，但COX-2表达与高微血管计数、VEGF表达及TP表达相关。通过对COX-2、VEGF和TP进行联合分析，至少有一个因子高表达的肿瘤微血管计数明显高于三个因子均低表达的肿瘤。与正常子宫内膜（n = 12）相比，我们通过RT-PCR证实子宫内膜癌（n = 17）中COX-2 mRNA表达上调。在这些肿瘤中，COX-2 mRNA表达与VEGF mRNA表达显著相关。COX-2在子宫内膜癌中上调，并通过与VEGF和TP相关的血管生成促进肿瘤生长。特异性抑制COX-2可能是子宫内膜癌一种有效的治疗干预措施。
