Chapple K S, Cartwright E J, Hawcroft G, Tisbury A, Bonifer C, Scott N, Windsor A C, Guillou P J, Markham A F, Coletta P L, Hull M A
Molecular Medicine Unit, Department of Histopathology, University of Leeds, St. James's University Hospital, Leeds, United Kingdom.
Am J Pathol. 2000 Feb;156(2):545-53. doi: 10.1016/S0002-9440(10)64759-1.
A putative target for the anti-colorectal cancer action of nonsteroidal anti-inflammatory drugs is the inducible isoform of cyclooxygenase (COX), COX-2. COX-2 is expressed within intestinal adenomas in murine polyposis models, but expression has been poorly characterized in human colorectal neoplasms. Therefore, we investigated the localization of the COX-2 protein in human sporadic colorectal adenomas. Immunohistochemistry for COX-2 and CD68 (a tissue macrophage marker) was performed on formalin-fixed, paraffin-embedded (n = 52) and frozen, acetone-fixed (n = 6) sections of human sporadic colorectal adenomas. Forty of 52 (77%) formalin-fixed adenomas expressed immunoreactive COX-2. COX-2 was localized to superficial interstitial macrophages in 39 cases (75%) and to deep interstitial macrophages in 9 cases (17%). COX-2 staining of dysplastic epithelial cells was observed in 15 cases (29%). A logistic regression analysis identified the adenoma site (P = 0.012) and histological type (P = 0.001) as independent predictors of superficial macrophage COX-2 expression. There was no relationship between the number of macrophages within an adenoma and macrophage COX-2 expression. These results indicate that COX-2 is expressed predominantly by interstitial macrophages within human sporadic colorectal adenomas. If COX-2 does indeed play a role in the early stages of colorectal carcinogenesis in man, these data suggest COX-2-mediated paracrine signaling between the macrophages and epithelial cells within adenomas.
非甾体抗炎药抗结直肠癌作用的一个假定靶点是环氧化酶（COX）的诱导型同工酶COX-2。在小鼠息肉病模型的肠道腺瘤中可检测到COX-2的表达，但在人类结直肠肿瘤中的表达特征尚不明确。因此，我们研究了COX-2蛋白在人类散发性结直肠腺瘤中的定位情况。采用免疫组织化学方法检测COX-2和CD68（一种组织巨噬细胞标志物）在人类散发性结直肠腺瘤福尔马林固定、石蜡包埋切片（n = 52）及冷冻、丙酮固定切片（n = 6）中的表达。52例福尔马林固定的腺瘤中，有40例（77%）表达免疫反应性COX-2。COX-2定位于39例（75%）腺瘤的表浅间质巨噬细胞及9例（17%）的深部间质巨噬细胞。15例（29%）发育异常的上皮细胞出现COX-2染色。逻辑回归分析显示，腺瘤部位（P = 0.012）和组织学类型（P = 0.001）是表浅巨噬细胞COX-2表达的独立预测因素。腺瘤内巨噬细胞数量与巨噬细胞COX-2表达之间无相关性。这些结果表明，COX-2主要在人类散发性结直肠腺瘤的间质巨噬细胞中表达。如果COX-2确实在人类结直肠癌发生的早期阶段发挥作用，这些数据提示腺瘤内巨噬细胞与上皮细胞之间存在COX-2介导的旁分泌信号传导。
