1994 Fiscal Year Final Research Report Summary
Alterations in oncogenes and tumor suppressor genes on human lung cancer as a treament guideline
| Project/Area Number |
04454351
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Thoracic surgery
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| Research Institution | KYUSHU UNIVERSITY (1994)
University of Occupational and Environmental Health, Japan (1992-1993) |
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Principal Investigator |
MITSUDOMI Tetsuya Kyushu University, Faculty of Medicine Research Associate, 医学部, 助手 (70209807)
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| Project Period (FY) |
1992 – 1994
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| Keywords | lung cancer / prognosis / p53 gene / rb gene / LOH / 3p / 9p / microsatellite polymorphism |
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| Research Abstract |
The objective of the present study is to investigate various genetic lesions in human lung cancer and to correlate the findings with clinicopathological features including patient prognosis.
First, we examined 120 cases of lung cancer operated on at the Fukuoka University and the University of Occupational and Environmental Health, Japan (UOEH) for p53 mutations. We showed that p53 mutations were a poor prognostic factor especially in advanced cases. However, this cohort was from two institutions and was not fully consecutive. The following analysis was performed using 129 patients out of 140 consecutive patients who were treated at the UOEH.
We examined this cohort for p53 abnormality at a DNA and protein level using immunohistochemistry and SSCP analysis, respectively. In this cohort, p53 mutations were a poor prognostic factor in adenocarcinoma, but there was no significant impact on survival in squamous cell carcinoma.
We then examined loss of heterozygosity at the 3p.5q, 9p locus usi
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ng a microsatellite polymorphism in collaboration with Dr.Adi Gazdar at the University of Texas. LOHs were found in 51,31 and 23%, respectively. Patients with 3p LOH had a poor prognosis in early stage group. However, the other lesions seemed not to be correlated with patient prognosis. Loss of expression of retinoblastoma gene was examined using immunohistochemistry in collaboration with Dr.William Benedict at the Baylor College of Medicine. This abnormality was found in 22% of cases, butthere was no relationship with patient prognosis.
Multivariate analysis for overall survival including above genetic lesions revealed that completeness of the resection was the only determinant for a poor prognosis. However, for a disease free interval in stage I patients, the multivariate analysis indicated that 3p LOH was the only significant predictor for an early disease relapse.
In conclusion, p53 and 3p may be useful markers for clinical oncology of lung cancer. However, there were no genetic prognostic indicator superior to the marker such as a disease stage which are being used routinely. Less
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