Sheehan Katherine M, Sabah Muna, Cummins Robert J, O'Grady Anthony, Murray Frank E, Leader Mary B, Kay Elaine W
Department of Pathology, Beaumont Hospital, Dublin, Ireland.
Hum Pathol. 2003 Dec;34(12):1242-6. doi: 10.1016/j.humpath.2003.01.001.
Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid to prostaglandins, prostacyclin, and thromboxane. COX-2 is expressed in many epithelial malignancies, particularly those of the gastrointestinal (GI) tract. COX-2 has been implicated in the pathogenesis of cancers and has a significant negative effect on survival. To date, little is known about the expression of COX-2 in nonepithelial tumors. The objective of this study was to evaluate the expression of COX-2 in GI stromal tumors (GISTs). We evaluated 15 GISTs using tissue microarray. Tissue blocks were retrieved and stained with hematoxylin and eosin to evaluate the histological tumor type. In addition, immunohistochemistry was performed for COX-2, the macrophage marker, CD68 (KP-1), and KIT (CD117). Two pathologists then evaluated the tissues to determine the extent and intensity of COX-2 expression. The location of CD68-positive cells, and whether these cells were COX-2 positive, was also evaluated. The results showed that 80% (12 of 15) of the tumors expressed COX-2. Expression was noted in the cytoplasm of the tumor cells, with variable intensity of staining among the tumors. COX-2 was expressed in both epithelial cell and spindle cell tumors, but appeared stronger in epithelial lesions. In mixed lesions, COX-2 was expressed to a greater extent in epithelial areas. There was a greater extent of COX-2 expression in malignant tumors and tumors located within the stomach. Tumor-infiltrating macrophages (CD68-positive cells) were identified in all of the lesions; in 80% of cases, those macrophages also expressed COX-2. This study is the first to demonstrate COX-2 expression in stromal lesions of the GI tract. The enzyme may play a role in the proliferation of these lesions, suggesting the potential use of nonsteroidal anti-inflammatory drugs in treatment.
环氧化酶（COX）是将花生四烯酸转化为前列腺素、前列环素和血栓素的关键酶。COX-2在许多上皮性恶性肿瘤中表达，尤其是胃肠道（GI）肿瘤。COX-2与癌症的发病机制有关，对生存率有显著负面影响。迄今为止，关于COX-2在非上皮性肿瘤中的表达知之甚少。本研究的目的是评估COX-2在胃肠道间质瘤（GISTs）中的表达。我们使用组织芯片评估了15例GISTs。检索组织块并用苏木精和伊红染色以评估组织学肿瘤类型。此外，对COX-2、巨噬细胞标志物CD68（KP-1）和KIT（CD117）进行免疫组织化学检测。然后由两位病理学家评估组织，以确定COX-2表达的程度和强度。还评估了CD68阳性细胞的位置以及这些细胞是否为COX-2阳性。结果显示，80%（15例中的12例）的肿瘤表达COX-2。在肿瘤细胞的细胞质中观察到表达，不同肿瘤之间染色强度不同。COX-2在上皮细胞肿瘤和梭形细胞肿瘤中均有表达，但在上皮性病变中表达更强。在混合性病变中，COX-2在上皮区域的表达程度更高。恶性肿瘤和位于胃内的肿瘤中COX-2表达程度更高。在所有病变中均发现肿瘤浸润巨噬细胞（CD68阳性细胞）；在80%的病例中，这些巨噬细胞也表达COX-2。本研究首次证明COX-2在胃肠道间质病变中的表达。该酶可能在这些病变的增殖中起作用，提示非甾体抗炎药在治疗中的潜在用途。
