p53 gene mutations and codon 72 polymorphism in ovarian carcinoma patients from Serbia.
OBJECTIVE
Ovarian cancer is the leading cause of death from gynecological malignancies. The early stages of this disease are asymptomatic and more than 75% of the cases are diagnosed with regional or distant metastases. p53 gene is frequently mutated in some histological subtypes of ovarian carcinomas. The role of p53 mutations and polymorphic variant of codon 72 in the prognosis of disease is still unclear. The aim of this study was to determine the frequency of p53 mutations and polymorphic variants of codon 72 among ovarian carcinoma patients and to correlate them with clinicopathological characteristics of disease.


METHODS
54 ovarian carcinoma patients were included in the study. DNA was isolated from tumor tissue by the salting- out method. p53 mutations in exons 4-8 were detected by PCR-SSCP (polymerase chain reaction - single-stranded conformational polymorphism) electrophoresis. Codon 72 polymorphism was assessed by RFLP (restriction fragment-length polymorphism) method.


RESULTS
p53 mutations were present in 11 out of 54 patients (20.4%). Twenty-four patients (44.4%) exhibited Arg/ Arg, 24 patients (44.4%) Arg/Pro and 6 patients (11.2%) Pro/ Pro genotype of 72 codon polymorphism. Correlations between p53 mutations and various clinicopathological characteristics were not found. However, we observed that the frequency of Pro/Pro genotype was increasing with higher histological grade as well as in advanced compared to localized disease, but without statistical significance. Distribution of p53 gene mutations between Pro/Pro genotype and Arg/Pro plus Arg/Arg genotypes was not statistically significant.


CONCLUSIONS
Our study suggests that Pro/Pro genotype of 72 codon polymorphism could be an independent prognostic marker in ovarian carcinomas.
Malisic
E
E
Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia. eminamalisic@yahoo.co.uk
Jankovic
R
R
Slavkovic
D
D
Milovic-Kovacevic
M
M
Radulovic
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D003062:Codon; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D055771:Serbia / Q000453:epidemiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D003062:Codon; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53