Kasper Hans-U, Wolf Hella, Drebber Uta, Wolf Helmut-K, Kern Michael-A
Department of Pathology, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50931 Koeln, Germany.
World J Gastroenterol. 2004 Jul 1;10(13):1918-22. doi: 10.3748/wjg.v10.i13.1918.
Cyclooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins. Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide. Both have constitutive and inducible isoforms. The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis, tumorigenesis and inflammatory processes. This study was to clarify their role in pancreatic adenocarcinomas.
We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocarcinomas of different grade and stage. The results were compared with microvessel density and clinicopathological data.
Twenty-one (52.5%) of the cases showed iNOS expression, 15 (37.5%) of the cases were positive for COX-2. The immunoreaction was heterogeneously distributed within the tumors. Staining intensity was different between the tumors. No correlation between iNOS and COX-2 expression was seen. There was no relationship with microvessel density. However, iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression. There was no correlation with other clinicopathological data.
Approximately half of the cases expressed iNOS and COX-2. These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas. Due to a low prevalence of COX-2 expression, chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success.
环氧化酶(COX)是将花生四烯酸转化为前列腺素的关键酶。一氧化氮合酶(NOS)是负责生成一氧化氮的酶。两者都有组成型和诱导型同工型。诱导型同工型(诱导型一氧化氮合酶和COX-2)作为肿瘤血管生成、肿瘤发生和炎症过程的调节因子备受关注。本研究旨在阐明它们在胰腺腺癌中的作用。
我们调查了40例不同分级和分期的胰腺导管腺癌中诱导型一氧化氮合酶和COX-2的免疫组化表达情况。将结果与微血管密度及临床病理数据进行比较。
21例(52.5%)病例显示诱导型一氧化氮合酶表达,15例(37.5%)病例COX-2呈阳性。免疫反应在肿瘤内分布不均。不同肿瘤的染色强度不同。未观察到诱导型一氧化氮合酶和COX-2表达之间的相关性。与微血管密度无关。然而,诱导型一氧化氮合酶阳性的肿瘤更常发生远处转移,恶性程度更高的肿瘤COX-2表达更高。与其他临床病理数据无关。
约半数病例表达诱导型一氧化氮合酶和COX-2。这两种酶似乎不是胰腺腺癌血管生成或致癌过程中的关键步骤。由于COX-2表达率较低,用COX-2抑制剂进行胰腺癌的化学预防只能取得有限的成功。