| Research Abstract |
Of the 30 esophageal squamous cell carcinoma (ESC) cell lines, 28 (93.3%) showed aberration of the p16 gene : Of the 15 primary esophageal tumors, aberrations of the p16 gene were detected in 7 (41%), while all cell lines derived from these tumors showed aberrations. We detected homozygous deletions in 9 cell lines which were established from tumors without them, and all of these deletions were observed even in cultures at early passage. These results suggest a possibility that cells exhibiting homozygous deletions in tumors expanded through the establishment of cell lines.
With regard to p53 mutation, of the 29 cell lines 22 (75.9%) showed p53 mutation. Compared with the results in these fresh tumor materials, the mutation incidence in cell lines was significantly high and the mutation spectrum was also different. In 7 cell lines established from mutation-free tumors, newly acquired mutations were detected in 5, which suggests that mutations might occur during the process of establishi
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ng cell lines.
The prognosis for patients with loss of APC locus, p53 mutation, CyclinD1 amplification and MDM2 amplification was significantly lower than that of patients without gene abnormality. Best predictability was obtained by a combined analysis of p53 mutation and MDM2 amplification. Loss of Rb gene revealed to be significant on the prognosis for patients, when a combined analysis of Rb and CyclinD1 gene was made.
Finaly, we checked the relation of gene abnormalities and histological effect of esophaegal cancer patients. Histological effect (grade>0) were noted in 62.5% (15/24) of the patients without p53 mutation, whereas, 6 out of 19 patients (31.6%) with p53 mutation had histological effect. The positive cases of immunohistochemical p53 staining in resected specimens and pre-treatment biopsy sample also tended to resist cisplatin. p53 mutation and its regulating genes may be a marker of chemosensitivity in esophageal SCC patients and chemotherapy may be selected according to the findings of p53 mutation and p53 regulating genes. Less
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