The Prognostic significance of p53 Gene Mutation and DNA Ploidy and Their Correlation in Advanced Epithelial Ovariasn Canser

Nam, Joo Hyun; Kim, Jong Hyeok; Kim, Yong Man; Kim, Young Tak; Mok, Jung Eun

Abstract

Ovarian cancer has a higher mortality rate than any other gynecologic malignancy and the majority of the patients are in an advanced stage at the time of diagnosis. However, well-estagblished clinicopahtological prognostic factiors such as stage, hisgologic type, grade of differentiation, amonut of residual tumor, and age are insufficient for prediction survival, thus necessitating new, more objective, and reproducible biological prognostic varialbes. Mutation of p 53 tumor suppressor gene and DNA aneuploidy are known to be associated with development and progression of ovarian cancer, but their prognostic sinificance is not yet conclusive. The objectives of this study were to define the nature and the prevalence of p53 gene mutation and DNA aneuploidy, and to deteirmine thier prognostic implications and their correlation in advanced epithelial ovarian cancer. the study population implications and of p53 tumor suppressor gene and DNA anuuploidy, and to determine their prognostic implications and their correlation in advanced epithelial ovarian cancer. The study population comprised tiryty-two patients with stage II to IV epithelial ovarian cancer who were mangaged at Asan Medical Center between may 1993 and April 1996. Fresh frozen tumor samples of primary lesion were analysed by direct DNA sequencing technique using ploymerase chain reaction with primers for exon 5,6,7 and 8. Measurerements of the nuclear DNA content were performed on the same cytometry. Twelve (37.5%) point mutations were identified in all exons, 3,2,2and 5 cases in exon 5,6,7and 8 of p 53 gene respectively without any preferential pattern of nucleotide substitution. Twenty-Three (71.9%) cased of tumors were revealed to be aneuploid (DNA index > 1.05). there was no correlation between p53 gene mutation and DNA ploidy. The presence or absence of p53 gene mutation had no signficant correlation with FIGO stge, histologic grade, serum CA 125 level after second chemotherapy and residual tumor size after debulking surgery. Two-year survival rates of patients with and with out mutation showed no difference. On the other hand, patients with aneuploid tumors revealed to be significantly associated with more advanced stage (P=0.46) and higher level of serum CA 125 after second chemotherapy (P=0.18) and had shorter 2-year survival rate than shose with diploid tumor, although the statistical significance was marginal (P=0.057). In conclusion, p53 gene mutation and DNA ploidy show no correlation, and p53 gene mutation does not appear to be a marker prediction the biological behavior or the outcome of the disease. However, DNA ploidy was shown to be utilized as a prognostic fatoc for survival in advanced epithelial ovarian cnacer, althour further studies for longer period of time are required to confirm.