Human colorectal adenomas demonstrate a size-dependent increase in epithelial cyclooxygenase-2 expression
Human colorectal adenomas demonstrate a size-dependent increase in epithelial cyclooxygenase-2 expression
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DOI：
10.1002/path.1232
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发表时间：
2002-12-01
影响因子：
7.3
通讯作者：
Paraskeva, C
中科院分区：
文献类型：
--
作者：
Elder, DJE;Baker, JA;Paraskeva, C
非甾体抗炎药对结直肠癌具有化学预防作用。这种作用部分归因于它们抑制环氧化酶（COX - 2）诱导型异构体的能力。然而，COX - 2在结直肠肿瘤发生的癌前阶段的细胞表达及作用尚不清楚。对35例人结直肠腺瘤和38例散发性浸润性结直肠腺癌中的COX - 2表达进行了评估。腺瘤按大小分为小（＜5mm）、中（5 - 9mm）和大（≥10mm）三类。所有组织均经石蜡包埋和福尔马林固定。采用免疫组织化学方法测定COX - 2蛋白表达。在38例癌中的35例（92%）上皮细胞以及8例（100%）淋巴结转移灶中检测到COX - 2。在35例癌中的30例（86%）以及所有淋巴结转移灶中，所有上皮细胞均表达COX - 2。35例腺瘤中有23例（66%）在肿瘤上皮中表达COX - 2。随着腺瘤大小增加（≥10mm），出现以下情况：（i）上皮中具有免疫反应性COX - 2的腺瘤比例增加（p = 0.036）——小腺瘤中为38%，大腺瘤中为82%；（ii）给定肿瘤内上皮COX - 2染色程度增加（p = 0.003）——在15%的小腺瘤和73%的大腺瘤中，100%的上皮细胞COX - 2呈阳性；（iii）上皮COX - 2染色强度增加（p = 0.009）——8.4%的小腺瘤和36%的大腺瘤出现强COX - 2染色。在相邻的正常上皮中未检测到COX - 2免疫反应性，但在相邻的正常组织、腺瘤和癌组织的成纤维细胞及炎性单核细胞中明显可见。这些结果表明，从腺瘤直径小于5mm开始，上皮COX - 2活性对腺瘤上皮细胞的生长和/或存活很重要，并且表达较高水平COX - 2的腺瘤上皮细胞具有选择性优势。版权所有，（C）2002约翰·威利父子有限公司
注：原文中“81,4”疑似有误，可能是“8.4”，翻译时按可能正确的理解进行了翻译。
Non-steroidal anti-inflammatory drugs are chemopreventive e for colorectal cancer. This effect is due in part to their ability to inhibit the inducible isoform of cyclooxygenase (COX-2). However, the cellular expression and role of COX-2 in the premalignant stages of colorectal tumourigenesis is unclear. COX-2 expression was assessed in 35 human colorectal adenomas and 38 sporadic invasive colorectal adenocarcinomas. Adenomas were classified as small (10 mm). All tissues were paraffin - embedded and formalin-fixed. COX-2 protein expression as determined using immunohistochemistry. COX-2 was detected in the epithelial cells in 35 of 38 carcinomas (92%) and in 8 of 8 (100%) lymph node metastases. All of the epithelial cells expressed COX2 in 30 of 35 (86%) carcinomas and in 100% or tile lymph node metastases. Twenty-three of 35 (66%) adenomas expressed COX-2 in the tumour epithelium. With an increase in the size of adenoma (10 mm), there was an increase in (i) the proportion of adenomas with immunoreactive COX-2 in the epithelium (p = 0.036) - this was 38% in small adenomas and 82% in large adenomas; (ii) the extent of epithelial COX-2 staining within a given tumour (p = 0.003) - 100% of epithelial cells were COX-2-positive in 15% of small adenomas and in 73% of large adenomas, and (iii) (fie intensity of epithelial COV 2 staining (p = 0.009) - strong COX-2 staining occurred in 81,4 of small adenomas and in 36% of large adenomas. COX-2 immunoreactivity was not detected in adjacent normal epithelium but was apparent in fibroblasts and inflammatory mononuclear cells of adjacent normal, adenoma, and carcinoma tissue. These results suggest that epithelial COX-2 activity is important for the growth and/or survival of adenomatous epithelial cells from an adenoma diameter of less than 5 mm and that there is a selective advantage for adenoma epithelial cells expressing higher levels of COX-2. Copyright, (C) 2002 John Wile Solis, Ltd.