| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
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.
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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
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