SPECIFIC GENETIC ANALYSIS OF PREMALIGNANT LESIONS OF THE PROSTATE USING SELECTIVE ULTRAVIOLET RADIATION FRACTIONATION TECHNIQUE
| Project/Area Number |
07671710
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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 |
Urology
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| Research Institution | UNIVERSITY OF TOKYO |
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Principal Investigator |
MATSUSHIMA Hisashi UNIVEERSITY OF TOKYO,DEPARTMENT OF UROLOGY,BRANCH HOSPITAL,FACULTY OF MEDICINE, 医学部・附属病院(分), 助手 (60157310)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | prostate cancer / PIN / p53 / PCR / SSCP / immunohistochemistry / apoptosis / p21 / DNA ploidy / immuno histochemistry / image cytometry / 前立腺癌 / cyclin p |
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| Research Abstract |
Objectives : To examine mutations of p53 tumor suppressor gene of specific cells constituting PIN and adenocarcinoma on hematoxylin eosin sections by selective ultraviolet radiation fractionation technique.
Materials and Methods : Reviewing HE sections from 80 radical prostatectomies and 20 autopsies, DNA specific for PIN,adenocarcinoma and benigh prostatic hyperplasia was extracted by SURF method (Shibata, 1993) and exons 4 to 9 of p53 gene were amplified by polymerase chain reaction and mutations were examined by single strand conformation polymorphism and direct sequencing. Ki-67, p53, bcl-2 and p21(WAF! ) were detected by immunohistochemistry and apoptosis was detected by TuUNEL method. The results were quantitatively assessed by CAS200 computer image nalysis system.
Results : Expression of wild p53 was detected in prostatic basal cells and the number of immunopositive cells decreased with advancing grade of PIN.P53 nuclear accumulation was detected in 20% of adenocarcinomas and LOH was detected in 12.5% of those. LOH was detected in 10% of PIN.Mutations of exon 4 in 2 adenocarcinomas, exon 5 in 6 and exon 7 in 2. There were no mutations found in low grade PIN.Ten percent of high grade PIN showed mutations all of which were concurrent with adenocarcinomas and showed a perfect concordance of mutation point with associated cancer.
Discussion : Mutations of p53 occurrs in a small subset of high grade PIN accompanying adenocarcinoma. However, there was no mutation found in PIN without adenocacinoma. Taking these into consideration, p53 gene alteration in PIN may be asubsequent event rather than a antecedant to prostatic carcinogenesis.
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Report
(4 results)
Research Products
(26 results)
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[Publications] Matsushima, H., Hosaka, Y., Suzuki, M., Mizutani, T., Ishizuka, H.and Kawabe, K.: "Bcl-2 Expression in Prostate Cancer and Its Relationship to Cell Cycle and Prognosis." International Journal of Urology. 3. 113-117 (1996)
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[Publications] Matsushima, H., Kitamura, T., Goto, T., Hosaka, Y., Homma, Y.and Kawabe, K.: "Combined Analysis with Bcl-2 and P53 Immunostaining Predicts Poorer Prognosis in Prostatic Carcinoma." The Journal of Urology. 158. 2278-2283 (1997)
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[Publications] Matsushima, H., Sasaki, T., Goto, T., Hosaka, Y., Homma, Y., Kitamura.T., Kawabe, K., Sakamoto, A., Murakami, T.and Machinami, R.: "Immunohistochemical Study of p21^<WAF1> and p53 Proteins in prostatic Cancer and Its Prognostic Significance." Human Pathology. 29, (in press). (1998)
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[Publications] Matsushima, H., Goto, T., Suzuki, M., Hosaka, Y., Homma, Y., Kitamura.T., Kawabe: "K.Analysis of Transition from Androgen-dependent to-independent State in Prostate Cancer. -Prognostic Impact of bcl-2 and p53 Immunostaining." Proceedings of the 23rd Annual Meeting of Japanese Society of Urologic Oncology. 15-18 (1997)
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