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난소종야에서 유세포 측정기를 이요한 DNA의 함량과 돌연변이형 p53 유전자 산물의 분석

Flow Cytometric Detction of Mutant p53 Gene Expression in Ovarian Malignanacy

대한산부인과학회지 1995년 38권 11호 p.2144 ~ 2156
이찬 (  ) - 고려대학교

이상도 (  ) - 고려대학교
최성원 (  ) - 고려대학교

Abstract


The incidence of ovarian carcinoma has been reported to increase in Korea. The majority of these cases occured in the over 45-age group. Because symptoms were initially vague, usually resulted in late presentation and diagnosis is often made in
more
advanced stages. Although progress in the efficacy of therapeutic modality has been achived in the last decade, prognosis is still poor. At the point of therapeutic view, assessment of a variety of prognostic factors is important and assessment
of
prognostic factors which can be measured objetively and have better reproducibility should preferably used. It is essential to identify prognostic factors of greater reliability than that are currenty available. A role for flow cytometry as a
means
of
quantitative analysis of cytology is emerging as a tool for diagnosis of cancer, specific histopathological diagnosis, prognosis and treatment. Aneuploidy of tumor DNA is considered to occur through marked enhancement of chromosomal instability.
As in the case of with other common human cancers, accumulation of multiple genetic alterations must be present in ovarian cancer, playing important roles in carcinogenesis and tumor progression. Characterized genetic alterations ranged from
proto-oncogene amplification to chromosomal deletions. Of those, deletion of chromosome 17p seems to be one of the most frequently involved, pointing to p53 as a potential matational target.
Recently, mutations of the p53 gene have been detected in many types of human cancer including ovarian cancer. Many evidences have suggested that P53 acts as tumor suppressor gene in wild-type form, where as mutant from had tumorigenic activity.
This study was designed to analyze DNA content using flowcytometry in fresh ovarian tumors and to evaluate p53 expression by direct fluorescent method in trypsinized, methanol fixed, fresh cell suspensions and by immunohistochemical staining. In
the
present study, over-expression of p53 were examined from surgical specimens of ovarian cancer in order to clarify the p53 gene abnormality. Clinicopathological parameters and tumor DNA ploidy pattern were examined in relation to p53 gene mutation
in
order to understand the role of p53 mutation in ovarian carcinogenesis.
@ES The obtained results are summaryzed as follows:
@EN 1. Expression of mutant from p53 protein was showed in 12 cases of 22(54.5%) ovarian cancers.
2. There was no correlation between expression of mutant from of p53 protein and clinicopathological factors such as histologic type, tumor grade and FIGO stage.
3. DNA aneuploidy was found in 11 cases of 20(50.0%) ovarian cancers(p<0.05).
4. A clear correlation was also demonstrated between the expression of mutant from p53 protein and an aneuploid pattern of tumor DNA(p>0.05).
In this study, there is no correlation between expression of mutant p53 protein and stage, or histological type or histological grade in ovarian cancer. There was significant relationship between p53 expression and aneuploidy in ovarian cancer.
It
is
suggested that the mutation of the p53 gene is associated with genesis and progression of ovarian cancer.

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