Mismatch Repair Status in the Endometrial Cancer Population: Prognostic Implications

Abstract

<h3>Purpose/Objective(s)</h3> Recent studies for endometrial cancer (EC) have demonstrated a divergence of outcomes based on mismatch repair (MMR) status, with MMR deficiency being an important predictor of recurrence and death. Further investigation is needed to validate these findings in additional patient populations to support the clinical significance of MMR status in EC. <h3>Materials/Methods</h3> We performed a single institution retrospective review at UMass Memorial Medical Center to identify EC patients with immunohistochemistry (IHC)-confirmed MMR status and to follow their clinical outcomes after definitive management (TAH/BSO with adjuvant chemotherapy and/or radiation therapy, as per NCCN guidelines). Querying the EPIC electronic medical record for all available years (2017-2021), we identified patients with ICD10 codes C54-C55. Of the total of 582 cases, 454 were endometrioid histology, 340 (75%) of which had MMR IHC results. Charts were reviewed longitudinally following completion of definitive management, and recurrences were assigned only if pathologically confirmed by tissue biopsy as malignancy of the same histological and/or IHC profile as tumor obtained at initial diagnosis. Initial stage, adjuvant treatment, recurrence patterns, and survival were compared between MMR-intact and MMR deficit cohorts. <h3>Results</h3> Of the 340 endometrioid patients with IHC confirmed MMR status, the majority were early-stage, node negative (92.6% Stage I, 2.9% Stage II, 4.4% Stage III), and all were eligible for upfront definitive management with TAH/BSO. Among the 340 patients, 86 (25%) were MMR-deficient, the majority of which were MLH1/PMS2 deficient. At a median follow up of 46 months, the recurrence rate in the MMR-deficient cohort (9.3%) was statistically significantly (p=0.005) higher than that of the MMR-intact cohort (4%), despite the higher proportion of MMR-deficient recurrent population receiving adjuvant radiation (75%) compared to the MMR-intact population (20%). None of the patients included in this study received adjuvant chemotherapy. The patterns of recurrence demonstrated a higher proportion of locoregional and distant disease within the MMR-deficient cohort (87.5%) compared to MMR-intact cohort (50%). There was a trend towards worse survival within recurrent MMR-deficient cohort compared to MMR-intact cohort (p=0.098). <h3>Conclusion</h3> Although the overall number of recurrence events was low, our endometrioid endometrial recurrent population demonstrates clear differences in rates of recurrence, patterns of recurrence and possibly even survival outcomes between MMR-intact and MMR-deficient cohorts, suggestive of worse prognosis for the MMR-deficient patient population. Future analyses will need to be completed to further describe the tumor characteristics at presentation, behavior of disease following recurrence and success of salvage treatment at the time of recurrence.