| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Esophageal squamous cell carcinoma (ESC) is a multistage progressive process that involves the conversion of normal squamous epithelium to that with basal cell hyperplasia (BCH), dysplasia that are thought to be precursor lesions of ESC, and then to invasive squamous cell carcinoma (S CC). It is speculated that the multistep process of accumulation of various genetic alterations correlates with the carcinogenesis of ESC. We studied five surgically resected superficial multifocal esophageal SCCs. p53 gene mutation, loss of heterozygosity (LOH), and microsatellite instability (MSI) were analyzed in SCC, BCH, dysplasia and normal esophageal epithelium, using DNA extracted from microdissected areas. Contact mutation and LOH of p53 gene were identified not only in SCC but also in dysplasia, BCH, and even in histologically normal epithelium. These findings indicated that aberrations of p53 gene are one of the key events in early phase of multistage carcinogenesis of ESCs. The high frequency
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of MSI and LOH of DNA mismatch repair gene were detected simultaneously in non-cancerous lesions and SCCs. These results supported that the deficiency of the mismatch repair system probably induces multifocal carcinogenesis of superficial ESCs. Furthermore, to evaluate the role of adhesion molecules in the progression and metastasis of ESCs, the correlation between the clinicopathological factors and the expression of various adhesion molecules (E-cadherin, β-catenin, integrin β1, CD44 and CD44v6) was studied in 71 primary tumors and their corresponding nodal metastases. Regarding the clinicopathological features, a reduced expression of adhesion molecules in primary tumors was found to be significantly associated with depth of invasion, lymph node metastasis, lymph and blood vessel permeations. The reduced expression of E-cadherin, β-catenin and CD44v6 in the metastatic lymph nodes was significantly correlated with the increased number of metastatic lymph nodes. The comprehensive analysis of various adhesion molecules not only in primary tumors but also in metastatic lymph nodes demonstrated that the alterations of adhesion molecules are important factors significantly influencing invasiveness, metastatic potential, and prognosis in ESCs. Less
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