Malisic E, Jankovic R, Slavkovic D, Milovic-Kovacevic M, Radulovic S
Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.
J BUON. 2010 Jan-Mar;15(1):101-6.
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.
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.
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.
Our study suggests that Pro/Pro genotype of 72 codon polymorphism could be an independent prognostic marker in ovarian carcinomas.
卵巢癌是妇科恶性肿瘤致死的主要原因。该疾病早期无症状，超过75%的病例在诊断时已出现区域或远处转移。p53基因在某些组织学亚型的卵巢癌中经常发生突变。p53突变及密码子72多态性变体在疾病预后中的作用仍不明确。本研究的目的是确定卵巢癌患者中p53突变及密码子72多态性变体的频率，并将它们与疾病的临床病理特征相关联。
54例卵巢癌患者纳入本研究。采用盐析法从肿瘤组织中分离DNA。通过聚合酶链反应-单链构象多态性（PCR-SSCP）电泳检测外显子4-8中的p53突变。采用限制性片段长度多态性（RFLP）方法评估密码子72多态性。
54例患者中有11例（20.4%）存在p53突变。24例患者（44.4%）表现为密码子72多态性的Arg/Arg基因型，24例患者（44.4%）为Arg/Pro基因型，6例患者（11.2%）为Pro/Pro基因型。未发现p53突变与各种临床病理特征之间存在相关性。然而，我们观察到与局限性疾病相比，Pro/Pro基因型的频率在组织学分级较高以及晚期疾病中有所增加，但无统计学意义。Pro/Pro基因型与Arg/Pro加Arg/Arg基因型之间p53基因突变的分布无统计学意义。
我们的研究表明，密码子72多态性的Pro/Pro基因型可能是卵巢癌的一个独立预后标志物。
