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KMID : 0603519980030010046
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Journal of Korean Association of Cancer Prevention
1998 Volume.3 No. 1 p.46 ~ p.57
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Genetic Instability as Biomarker during Multistep Tumorigenesis in Cervical Cancer
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Mitchell M.F
Hittelman W.N.
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Abstract
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Background: Cervical cancer is the second most common malignancy in women worldwide. Chemoprevention of cervical cancer is highly desirable to reduce incidence and prevalence of cervical cancer, Biomarkers for chemoprevention are essential to develop successful chemoprevention trials.
Purpose: to better understand the field cancerization and multistep tumorigenesis process in cervical intraepithelial neoplasia and invasive cancer of the cervix, we examined chromosome 9 polysomy in tissues that changed from histologically normal epithelium through cervical intraepithelial neoplasia to invasive cancer of the cervix.
Methods: 37 specimens from the same number of patients were studied. These specimens show transition from normal to CIN-3 - invasive cancer. Hybridization with DNA probes specific for the centromeric region of chromosome 9 was performed. A pathologist marked each pathological area. At least 200 nuclei were scored for each defined histological area for number of chromosomes.4 chromosome index was obtained dividing the total number of signal spots by the number of nuclei analyzed. Differences for each specific pathological entity means were analyzed.
Results: An increase in the normalized chromosome index was present as the tissue progressed from normal to cervical intraepithelial neoplasia to invasive carcinoma. The frequency of cells with polysomy increased as the tissues progressed. Genotypic abnormalities adjacent to the tumor were present.
Conclusions: The determination of the degree of accumulated genetic abnormalities in cervical tissue may be useful for identifying individuals with high risk of progression to cervical cancer This parameter may be a biomarker as an intermediate end-point in chemoprevention trials.
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KEYWORD
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Cervical cancer, Biomarkers, Genetic instability, Tumorigenesis, Chemopreventio
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