Relation of COX-2 in carcinogenesis and invasion and metastasis of oral cancer

环氧合酶(COX)-2在肿瘤发生、侵袭和转移中的作用尚不清楚。为探讨环氧合酶-2(COX-2)在口腔癌中的表达是否可以作为判断肿瘤进展、侵袭和转移的指标，本研究采用免疫组织化学方法检测221例口腔癌前病变和口腔癌(包括原位癌、浸润性鳞癌和未分化癌)中COX-2蛋白的表达，并以正常口腔鳞状上皮为对照。相反，约60%的上皮内异型增生、83%的异型增生和所有的浸润性癌COX-2表达增加，α标记指数(LI)作为细胞增殖的标志。有趣的是，COX-2在口腔癌肿瘤侵袭的发育灶中有较高的表达。…COX-2蛋白的高表达与DNA-Topo IIαLI升高密切相关，提示COX-2可能参与了肿瘤的恶性转化和生长。同时表达COX-2和DNA-Topo IIα的患者预后较差。因此，我们认为COX-2与肿瘤的侵袭性有关，COX-2的表达可能成为口腔癌患者预后的一个指标。另一方面，我们研究了COX-2蛋白的表达与口腔癌局部淋巴结转移和患者预后的关系。应用免疫组织化学方法检测COX-2蛋白在口腔鳞癌和未分化癌中的表达及DNATOPO IIα活性。以20例正常口腔鳞状上皮细胞为对照。结果显示，COX-2的表达随着DNA-Topo IIαLI的升高而增加。原发肿瘤中COX-2表达增加伴DNA-Topo IIαLI升高在LN(+)组比LN(-)组更频繁、更强烈(p&lt；0.05)。在LN(+)组中，与原发灶相比，56例(80%)患者转移灶中COX-2表达增加，DNA-Topo IIαLI升高(p&lt；0.01)。此外，42例(75%)COX-2高表达伴DNA-Topo IIαLI升高的患者预后较差。因此，COX-2的表达可能成为口腔癌转移的一个指标，并可能反映口腔癌患者的预后。较少

The role of cyclooxygenase (COX)-2 in carcinogenesis, invasiveness and metastasis is unclear. In this research, to determine whether COX-2 expression could serve as an indicator of progression of tumor, invasiveness and metastasis in oral carcinoma, we mainly examined the immunohistochemical expression of COX-2 protein with the analysis on cell proliferative activity in 221 cases of oral precancerous disease and oral cancer including carcinomas in situ (CISs), invasive squamous cell carcinomas and undifferentiated carcinomas.As the results, normal squamous epitheliums that used as control showed no COX-2 expression. In contrast, approximately 60% of intraepithelial dysplasias, 83% of CISs, and all of invasive carcinomas demonstrated increase COX-2 expression with elevated DNA-Topoisomerase (Topo) IIα laballing index (LI) as cell proliferating marker. As an interestingly fact, a high intensity of COX-2 expression was observed in the developmental foci with tumor invasion of oral cancer. … More Increased expression of COX-2 protein correlated with elevated DNA-TopoIIαLI, indicating that COX-2 may contribute to malignant transformation and tumor growth. Furthermore, the patients with expression of both COX-2 and DNA-TopoIIα showed poor outcome. Therefore, it was considered that the COX-2 related to tumor invasiveness, and was suggested that the COX-2 expression become a possible indicator in the outcome in patients with oral cancer.On the other hand, we examined the relationship between the expression of COX-2 protein with cell proliferative activity in regional lymph nodes metastasis and outcome inpatients with oral cancer. Expression of COX-2 protein and DNA-TopoIIα activity were evaluated by immunohistochemical technique in eacn 70 of oral squamous cell carcinomas and undifferentiated carcinomas of primary with or without regional lymph node (LN) metastatic lesions. Twenty normal oral squamous epitheliums were used as control. In the result, increased COX-2 expression withelevated DNA-TopoIIαLI. Increased COX-2 expression with elevated DNA-TopoIIα LI in the primary tumors was more frequent and intense in the LN(+) group than in the LN(-) group (p<0.05). In the LN(+) group, 56 (80%) patients also showed a similar increased COX-2 expression with elevated DNA-TopoIIαLI in the metastatic lesions, compared with the primary lesions (p<0.01). Furthermore, 42 (75%) patients with increased COX-2 expression with elevated DNA-TopoIIαLI had poor outcome. Therefore, it was suggested that the COX-2 expression become a possible indicator in the metastasis of oral cancer and might reflect on the outcome of the patients with oral cancer. Less