| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1998: ¥8,400,000 (Direct Cost: ¥8,400,000)
|
|---|
| Research Abstract |
A molecular staging protocol using reliable markers is of importance in predicting the prognosis of patients with non-small cell lung cancer (NSCLC) and for instituting their appropriate post-surgical treatment. We analyzed tumor tissues from 296 NSCLC patients. The DNA and mRNA were extracted from frozen specimens, and then polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to investigate mutations of p53 from exons 5 to 8, and mutations of K-ras at exon 1. Mutations of p53 gene occurred in 36.5% of patients, and mutations of the K-ras gene occurred in 8.8%. To determine MRP-1/CD9 gene and KAI1/CD82 gene expression, which have been postulated to be metastasis suppressor genes, we have applied quantitative RT-PCR. We found that 114 patients (38.5%) had MRP-1/CD9-reduced tumors, and that 216 patients (72.9%) had KAI1/CD82-reduced tumors. In addition, the immunohistochemical analysis for p16 protein was performed. One hundred
… More
seven carcinomas (36.1%) were classified as p16 negative. P16-negative tumors in squamous cell carcinomas were significantly more than those in adenocarcinomas (P=0.039). Moreover, immunohistochemistry was performed to evaluate bcl-2 and bax expression, One hundred fifteen carcinomas (38.9%) were bcl-2-positive and 213 carcinomas (80.0%) were bax-positive, However, there was no difference in bcl-2 expression in relation to p53 status. On the other hand, tumors with structural mutations of p53 had significantly lower expression of bax than those with wild-type p53 (P=0.0026). In contrast, tumors with mutations of the loop-sheet-helix motif of p53 had significantly higher expression of bax than those with wild-type p53 (P=0.0236). The frequency of a bcl-2/bax ratio of 【greater than or equal】1 was significantly lower in tumors with mutations of the loop-sheet-helix motif than that in tumors with wild-type p53 (P=0.0240). Mutations of the loop-sheet-helix motif of p53 were correlated with overexpression of bax, while other mutations of p53 were correlated with low levels of bax expression. This variation in pattern of bax expression in relation to mutant p53 might reflect the biological behavior of tumors in patients with bcl-2-positive NSCLCs. Up to date, there was no significant difference in survival according to these tumor markers status and further examination are needed to establish whether they are indeed of practical utility as prognostic predictors. Less
|
