Fig 1.
Representative examples of immunohistochemistry staining for the four MMR proteins.
Tumors with MLH1-deficiency (dMLH1) show negative expression in both MLH1 and PMS2 IHC, those with MSH2-deficiency (dMSH2) show negative expression in both MSH2 and MSH6 IHC, with PMS2-deficiency (dPMS2) they show negative expression only in PMS2, and tumors with MSH6-deficiency show negative expression only in MSH6.
Table 1.
Association between clinic-pathological features and EC patients stratified by genetic mutational profiles.
Fig 2.
Methylation analysis of the promoter region in the MLH1 gene.
(A) Schematic depiction of two regions (5’-region and 3’-region) of the MLH1 promoter for methylation and results of a panel of representative fluorescent bisulfite PCR following restriction enzyme analysis. Methylated samples had the new fragment cleaved by the restriction enzyme. (B) The frequencies of MLH1 promoter methylation according to MLH1 expression status. The top panel shows the results of the MLH1-5’ region, the middle panel shows the MLH1-3’ region and the bottom panel shows partial (i.e. only MLH1-5’ methylation) and extensive methylation (i.e. both MLH1-5’ and -3’ methylation).
Fig 3.
Detection of MSI and distribution of number of MSIs in 138 EC patients.
(A) Example of MSI and non-MSI cases analyzed by four mononucleotide repeat markers (BAT26, NR21, NR27, and CAT25). (B) Association between MSI, POLE mutation, MLH-1 promoter methylation and MMR protein expression. The number of mononucleotide repeat markers showing MSI are shown by color.
Fig 4.
Molecular and clinic-pathological features of 138 ECs.
(A) Molecular and clinic–pathological landscape of 138 ECs. Genetic analysis, focusing on frequent hotspot mutations in the POLE gene, and MSI status result in the identification of three molecular subgroups: (1) POLE-mutant, (2) MSI and (3) non-MSI. (B) Progression-free survival and endometrial cancer-specific survival of 138 EC patients stratified by genetic profiles. P values were calculated by the log-rank test.
Table 2.
Univariate and multivariate outcome analyses of 138 EC patients.