2006 Fiscal Year Final Research Report Summary
Analysis of tumorigenicity of the endometrium by selective estrogen receptor modulators
| Project/Area Number |
17591768
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | University of Occupational and Environmental Health, Japan. (2006)
Fukuoka University (2005) |
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Principal Investigator |
HACHISUGA Toru University of Occupational and Environmental, Professor, 医学部, 教授 (70180891)
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| Project Period (FY) |
2005 – 2006
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| Keywords | K-ras / tamoxifen / endometrium / polyp / Ki-67 / apoptosis |
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| Research Abstract |
Back ground and aims : A high incidence of the endometrial K-ras mutation in Tamoxifen (TAM)-treated breast cancer patients has been reported. We examined the changes in the K-ras mutations after the cessation of TAM treatment and the correlation between K-ras mutation and apoptosis.
Methods : DNA was extracted from fresh cytologic or polypectomy samples of the endometrium. Mutations were detected by enriched PCR and an enzyme-linked mini-sequence assay (ELMA). Apoptotic cells were identified using a modified terminal deoxynucleotidyltransferase-biotin nick end-labelling (TUNEL) method.
Results : The monitoring of the K-ras codon 12 mutations was done in the 28 tamoxifen (TAM)-treated patients ranging from 2 years to 6 years. K-ras mutations were detected in 13 patients, while they were not detected in 15 patients in the initial examination. Among 13 patients with K-ras mutation, the repeated examination has been detected no K-ras mutation in more than 2 years after the cessation of TAM treatment. Fifteen patients without K-ras mutation have not demonstrated any K-ras mutation in repeat examinations. The correlation between K-ras mutation and apoptosis was examined in the 31 TAM-treated postmenopausal endometrial polyps. K-ras mutations were detected in 9 endometrial polyps and were not in 22 endometrial polyps. The mean of the apoptotic index was 3.8 in endometrial polyps with K-ras mutation and 1.0 in endometrial polyps without K-ras mutation, (P<0.001).
Conclusions : K-ras mutation may be removed from the endometrium after cessation of TAM treatment with enhanced apoptosis.
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