1995 Fiscal Year Final Research Report Summary
Analyzes of p16/CDKN2.p53 and ras gene mutations with cell-proliferative activities in oral squamous cell carcinomas and the premalignant lesions
| Project/Area Number |
06672011
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Surgical dentistry
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| Research Institution | Nara Medical University |
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Principal Investigator |
SUGIMURA Masahito Nara Medical University, Department of Oral and Maxillofacial Surgery, Professor, 医学部, 教授 (20028749)
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| Co-Investigator(Kenkyū-buntansha) |
KITAHORI Yoshiteru Nara Medical University, 2nd Department of pathology Assistant, 医学部, 助手 (30221211)
KIRITA Tadaaki Nara Medical University, Department of Oral and Maxillofacial Surgery, Lecturer, 医学部, 講師 (70201465)
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| Project Period (FY) |
1994 – 1995
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| Keywords | oral tumor / premalignant / cell proliferation / p16 / CDKN2 / p53 / ras |
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| Research Abstract |
p16/CDKN2, p53 and ras gene mutations were examined using a combination of immunohistochemistry and SSCP-Sequence analyzes with cell proliferative activities such as PCNA and AgNOR in 20 oral squamous cell carcinomas and 20 oral premalignant lesions. The p16/CDKN2 gene mutations were found 2 of 20 cases squamous cell carcinoma, but none of premalignant lesions. Two cases with p16/CDKN2 gene deletions were detected with immunonegative staining for p16 protein. The p53 gene mutations were found 5 of 20 squamous cell carcinoma and none of premalignant lesions. A mutation in the K-ras gene was found in single carcinoma and dysplastic samples.
On the other hand, 35% (7/20) of the oral squamous cell carcinomas demonstrated immunoreactivity for p53 and 50% were immunopositive for ras p21. Two cases with positive staining for p53 in moderate dysplasia and hyperplasia, without p53 gene mutation, were relatively light and seemed to be limited to a few cells within the basal cell layr. PCNA and AgNOR values revealed high scores in these cases, it is suggested that p53 expression may be related to accumulation of wild type protein with rapid cell proliferation rather than gene mutation. The PCNA and AgNOR score tend to be significantly higher in the carcinomas than those in premalignant lesions. From the data, it can be argued that p16/CDKN2 and p53 mutations are relatively late occurrences and that genetic alterations of the ras genes may not play a significant role in human oral tumorigenesis. The tumor suppressor gene such as p16/CDKN2 or p53 seem to be not only independently occurred but involved in later events of oral tumorigenesis.
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