PURPOSE: The present study aims to assess the incidence of microsatellite instability (MSI) and mutations in the PTEN and beta-catenin (CTNNB1) genes in endometrial carcinomas and to analyze the detected defects in these factors in relation to each other and to the clinico-pathological features of tumors. MATERIALS AND METHODS: In a series of 56 endometrioid endometrial carcinomas, the status of MSI was determined using nine polymorphic markers, and mutations in all exons of the PTEN gene and in exon 3 of the CTNNB1 gene were evaluated by SSCP and sequencing methods. RESULTS: Microsatellite instability was found in 18 carcinomas (32.1%, MSI+); the remaining 38 tumors were microsatellite stable (MSI-). In 15 cases (26.8%), a loss of heterozygosity (LOH) at the studied microsatellite markers also occurred. In 29 carcinomas (51.8%), mutations were found in the PTEN gene and in nine tumors (16.1%) in the CTNNB1 gene. PTEN mutations occurred significantly more frequently in MSI+ than in MSI- tumors (77.8 vs. 39.5%, p = 0.007), but, except for one, none of them was attributable to MSI. In contrast, incidence of CTNNB1 mutations in MSI+ and MSI- tumors no significantly differed between themselves (16.7 vs. 15.8%, p = 0.760). Interestingly, mutations in the CTNNB1 gene most frequently coexisted with mutations in the PTEN gene (7/9, 77.8%). However, this finding requires future verification on a larger group of cases. The incidence of MSI and PTEN, but not CTNNB1 mutations, was significantly more common in poorly, than in well-to-moderately, differentiated tumors (G3 vs. G1 + G2; p = 0.042, 0.039 and 0.958, respectively). CONCLUSION: We conclude that most frequently occurring mutations in the PTEN gene may be a key event for the tumorigenesis of endometrioid endometrial carcinomas, while coexistence or absence of microsatellite instability or mutations in the CTNNB1 gene may reflect the heterogeneity of molecular mechanisms contributing to the development of these tumors.
PURPOSE: The present study aims to assess the incidence of microsatellite instability (MSI) and mutations in the PTEN and beta-catenin (CTNNB1) genes in endometrial carcinomas and to analyze the detected defects in these factors in relation to each other and to the clinico-pathological features of tumors. MATERIALS AND METHODS: In a series of 56 endometrioid endometrial carcinomas, the status of MSI was determined using nine polymorphic markers, and mutations in all exons of the PTEN gene and in exon 3 of the CTNNB1 gene were evaluated by SSCP and sequencing methods. RESULTS: Microsatellite instability was found in 18 carcinomas (32.1%, MSI+); the remaining 38 tumors were microsatellite stable (MSI-). In 15 cases (26.8%), a loss of heterozygosity (LOH) at the studied microsatellite markers also occurred. In 29 carcinomas (51.8%), mutations were found in the PTEN gene and in nine tumors (16.1%) in the CTNNB1 gene. PTEN mutations occurred significantly more frequently in MSI+ than in MSI- tumors (77.8 vs. 39.5%, p = 0.007), but, except for one, none of them was attributable to MSI. In contrast, incidence of CTNNB1 mutations in MSI+ and MSI- tumors no significantly differed between themselves (16.7 vs. 15.8%, p = 0.760). Interestingly, mutations in the CTNNB1 gene most frequently coexisted with mutations in the PTEN gene (7/9, 77.8%). However, this finding requires future verification on a larger group of cases. The incidence of MSI and PTEN, but not CTNNB1 mutations, was significantly more common in poorly, than in well-to-moderately, differentiated tumors (G3 vs. G1 + G2; p = 0.042, 0.039 and 0.958, respectively). CONCLUSION: We conclude that most frequently occurring mutations in the PTEN gene may be a key event for the tumorigenesis of endometrioid endometrial carcinomas, while coexistence or absence of microsatellite instability or mutations in the CTNNB1 gene may reflect the heterogeneity of molecular mechanisms contributing to the development of these tumors.
Authors: D Kong; A Suzuki; T T Zou; A Sakurada; L W Kemp; S Wakatsuki; T Yokoyama; H Yamakawa; T Furukawa; M Sato; N Ohuchi; S Sato; J Yin; S Wang; J M Abraham; R F Souza; K N Smolinski; S J Meltzer; A Horii Journal: Nat Genet Date: 1997-10 Impact factor: 38.330
Authors: Helga B Salvesen; Ingunn Stefansson; Ellen I Kretzschmar; Paula Gruber; Nicola D MacDonald; Andy Ryan; Ian J Jacobs; Lars A Akslen; Soma Das Journal: Int J Oncol Date: 2004-12 Impact factor: 5.650
Authors: O Aprelikova; J Palla; B Hibler; X Yu; Y E Greer; M Yi; R Stephens; G L Maxwell; A Jazaeri; J I Risinger; J S Rubin; J Niederhuber Journal: Oncogene Date: 2012-08-13 Impact factor: 9.867
Authors: Dawne N Shelton; Hubert Fornalik; Traci Neff; Soo Yeun Park; David Bender; Koen DeGeest; Xiaoming Liu; Weiliang Xie; David K Meyerholz; John F Engelhardt; Michael J Goodheart Journal: PLoS One Date: 2012-07-06 Impact factor: 3.240
Authors: H Gbelcová; P Bakeš; P Priščáková; V Šišovský; I Hojsíková; Ľ Straka; M Konečný; J Markus; C W D'Acunto; T Ruml; D Böhmer; Ľ Danihel; V Repiská Journal: Anal Cell Pathol (Amst) Date: 2015-05-31 Impact factor: 2.916