|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1992 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1991 : ¥700,000 (Direct Cost : ¥700,000)
Alterations of functional genes associated with cellular proliferation and differentiation that are called oncogenes or proliferation and differentiation that are called oncogenes or tumor suppressor genes, are required during oncogenesis. The sequential multistages of tumor progression are analyzed, associated with the possible events thata modulate property and heterogeneity of tumor cells, such as cellular proliferation, invasion and metastasis.
We investigated the prognostic significance of mutations of ras gene and p53 gene, as putative oncogene and tumor suppressor gene, respectively. In 115 patients with adenocarcinoma of the lung, the ras mutations were detected in 18 cases (15.7%), using polymerase-chain-reaction (PCR) technique. Of the completely resected patients without lymph node metastasis, the 5-year survival rate in those with the ras mutations was 53.3%, compared with 83.6% in those without the ras mutations. In 79 patients with non-small cell lung cancer, the p53 mutations were detected in 25 cases (31.6%) and the presence of the p53 mutations was associated with a shortened survival even in stage I of the disease. On the other hand, we investigated the incidence of the second primary carcinomas for surgically treated lung cancer patients with the ras mutations. One was a synchronous carcinoma of the larynx, and 3 metachronous carcinomas of the lung, trachea and stomach. The ras mutations were also detected in the two second primary carcinomas of the lung and trachea, but the p53 mutations did not.
In this study, our data revealed that the mutations of ras gene and p53 gene were associated with the shorted survival. These mutations were closedly related to not only the tumor progession of the lung, but also the oncogenesis of the second primary carcinoma. These molecular biological methods might be useful to define a certain lung cancer patient as suitable condidates for investigational therapeutic approarches.