STUDY OF TUM0R SUPPRESSOR GENE AND ANGIOGENESIS IN ORAL CAJNCER -Effect of the transfection of p53 and p16 tumor suppressor genes on angiogenesis-.

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671937
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: OKAYAMA UNIVERSITY
• Principal Investigator: KISHIMOTO Koji OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, lNSTRUCTOR, 大学院・医歯学総合研究科, 助手 (40243480)
• Co-Investigator(Kenkyū-buntansha): MESE Hiroshl OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, lNSTRUCTOR, 大学院・医歯学総合研究科, 助手 (40325098) ; SASAKI Akira OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (00170663)
• Project Period (FY): 2000 – 2001
• Keywords: oral squamous cell carcinoma / tumor suppressor gene p16 and p53 / angiogenic factor / VEGF / PD-ECGF / VEGF-C

Research Abstract

I) Effect of tumor suppressor gene p53 and p16 on angiogenesis
As a result of SCC cell lines, HSC-4 was mutated R74 (CGA) to end codon (TGA) in exon 2 and SCC-4 was detected in the deletion of exon 2/3 splice acceptor site. They showed strong expression of VEGF.
II) Expression of angiogenic factor and tumor suppressor gene, and their clinicopathological implications in oral squamous cell carcinomas
We investigated the expression of VEGF, PD-ECGF, VEGF-C, p53 and p16, and their clinicopathological implications in oral squamous cell carcinomas by immunohistochemistry. Intratumor microvessel density was evaluated with the number of positive microvessels for CD31 antibody. Results : VEGF-C expression correlated with lymph node metastasis (p < 0.01). According to stepwise logistic regression analysis, univarate analysis showed lymph node metastasis correlated with mode of invasion, VEGF-C expression and vessel invasion (p < 0.05). Moreover, multivariate analysis revealed that mode of invasion and VEGF-C expression were the exclusive indipendent factors influencing lymph node metastasis (p < 0.05). PD-ECGF correlated with, intratumor microvessel density (p < 0.05). VEGF, tumor differentiation, mode of invasion and lymph node metastasis were found to be significant in survival probability (p < 0.05), and VEGF and lymph node metastasis were independent prognostic factors in the Cox's multivariate proportional hazard model. Conclusions : It was suggested that the expression of VEGF, PD-ECGF, and VEGF-C in oral squamous cell carcinoma mainly correlated with prognosis, angiogenesis, lymph node metastasis respectively. However, tumor suppressor gene p53 and p16 did not correlate with metastasis and prognosis.