TP53 mutations in endometrial cancers: relation to PTEN gene defects.
The PTEN and TP53 genes participate in the carcinogenesis of many malignancies, but the role of both genes in endometrial carcinogenesis is not fully elucidated. The aim of the study was to determine the quality and the frequency of incidence of TP53 and PTEN gene mutations and to assess their coexistence in endometrial cancers. Besides that, the correlation was studied between the detected defects and clinicohistopathological characteristics of the studied endometrial cancers. The study material included DNA isolated from 81 endometrial cancers. The incidence of TP53 and PTEN gene mutations was assessed using polymerase chain reaction-single-strand conformation polymorphism and sequencing techniques. The statistical analysis of the results was performed using [chi]2 test. In 64.2% of the 81 endometrial cancers, mutations occurred in TP53 and/or PTEN genes: in 16.1%, mutations occurred only in TP53; in 33.3%, only in PTEN gene; and in 14.8%, in both TP53 and PTEN genes. In 35.8% of cases, no mutations were found in these genes. No statistically significant relationship was found between the incidence of mutations in TP53 gene and that in PTEN gene (P = 0.986). The incidence of mutations in PTEN gene was higher in medium and poorly differentiated endometrial cancers than in well-differentiated ones and was statistically significant (G2 + G3 vs G1; P = 0.049). Besides that, mutations in PTEN gene occurred significantly more frequently in patients younger than 55 years than in older women (> or =55 years; P = 0.027). No similar differences were found in TP53 gene. The results of the study demonstrate that TP53 gene mutations occur in some of endometrioid endometrial cancers in the presence of PTEN gene mutations, suggesting that both these genes participate in the development of these tumors.