|Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
The molecular biological degree of tumor malignancy and its clinical significance were examined in paraffin-enbedded specimens of carcinoma of the gallbladder and the bile duct. The nuclear DNA ploidy pattern was measured using flow cytometry, and immunohistochemical staining of cancer cells was performed by the avidin-biotin peroxidase complex (ABC) method for the following factors : proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), c-erbB-2, c-myc, K-ras, p53, fibronection, laminin and tenascin.
1. Carcinoma of the gallbladder : Patients with aneuploid and/or K-ras-positive tumors showed a significantly higher incidencd of advanced carcinoma and a significantly lower survival rate than those with diploid and/or K-ras-negative tumors. In patients with depth of cancer invasion to the subserosal layr or more, expression of K-ras provided more significant prognostic information than histopathological factors. All patients who had tumors that were aneuploe
d and PCNA-positive, c-myc-positive and P53-positive, or tenascin-positive and fibronectin-negative died of tumor recurrence within 2 years. Moreover, the PCNA labeling index and the expression of extracellular matrix were considered to be valuable indicators of the time and mode of tumor recurrence after radical resection.
Carcinoma of the bile duct : In all patients who survived more than 3 years, nuclear DNA ploidy pattern showed diploid type and the PCNA labeling index were less than 30%. On other hand, in patients who died of tumor recurrence within 3 years, 42.9% were aneuploid tumors, and the positive rates of EGFR and tenascin were significantly lower than in patients survived more than 3 years. According to the correlation between the expression of extracellular matrix and the mode of tumor recurrence after radical resection, in patients with laminin-positive tumors the incedence of liver and/or lung metastasis after radical resection was significant higher than in laminin-negative tumors. Less