Impact of mismatch repair genes deficiency on survival outcomes and establishment of a novel prognostic prediction model for stage I-II endometrial carcinoma.
Pathological characteristics and MMR status can be determined from microscopic indicators and immunohistochemical (IHC) staining of surgical specimens, and these approaches are more cost-effective and convenient than genome profiling tests. We aimed to evaluate the impact of MMR deficiency on survival outcomes and build a new prognostic model for early-stage endometrial carcinoma (EC) patients.
Patients with stage I to II EC who underwent hysterectomy followed by adjuvant radiotherapy from Oct. 2017 to Dec. 2020 at our institution were retrospectively reviewed. Tumor MMR status was routinely tested by IHC. According to MMR status, they were classified into intact MMR (MMRp) group and defective MMR (MMRd) group.
Patients were classified into MMRp group (n = 207) and MMRd group (n = 69). Compared with those in the MMRp group, patients in the MMRd group were more likely to have high-grade disease, LVSI, and high-intermediate risk (HIR)-to-high risk (HR) classifications. The 3-year CSS, DFS, and DMFS rates were significantly lower in the MMRd group. When patients were stratified by risk group, DFS and DMFS were significantly worse among MMRd patients in the HIR-to-HR group. Regarding failure patterns, MMRd patients were more likely to experience distant failure. Among 276 patients, multivariate Cox analysis revealed that ER or PR status, myometrial invasion (MI), MMR status, and LVSI were independent prognostic factors for DFS, whereas ER or PR status, MMR status, and MI were significant predictors of DMFS. A prediction model combining the MMR status and the significant prognostic predictors mentioned above in the multivariate analysis was built through nomogram models.
Among early-stage EC patients, MMRd group had poorer survivals. Combination of MMR status and other clinicopathological factors could establish a new prognostic model. Prospective studies with full molecular sequencing to determine the prognostic significance of MMR status are needed.
Patients with stage I to II EC who underwent hysterectomy followed by adjuvant radiotherapy from Oct. 2017 to Dec. 2020 at our institution were retrospectively reviewed. Tumor MMR status was routinely tested by IHC. According to MMR status, they were classified into intact MMR (MMRp) group and defective MMR (MMRd) group.
Patients were classified into MMRp group (n = 207) and MMRd group (n = 69). Compared with those in the MMRp group, patients in the MMRd group were more likely to have high-grade disease, LVSI, and high-intermediate risk (HIR)-to-high risk (HR) classifications. The 3-year CSS, DFS, and DMFS rates were significantly lower in the MMRd group. When patients were stratified by risk group, DFS and DMFS were significantly worse among MMRd patients in the HIR-to-HR group. Regarding failure patterns, MMRd patients were more likely to experience distant failure. Among 276 patients, multivariate Cox analysis revealed that ER or PR status, myometrial invasion (MI), MMR status, and LVSI were independent prognostic factors for DFS, whereas ER or PR status, MMR status, and MI were significant predictors of DMFS. A prediction model combining the MMR status and the significant prognostic predictors mentioned above in the multivariate analysis was built through nomogram models.
Among early-stage EC patients, MMRd group had poorer survivals. Combination of MMR status and other clinicopathological factors could establish a new prognostic model. Prospective studies with full molecular sequencing to determine the prognostic significance of MMR status are needed.