Search

Objectives: Endometrial cancer due to loss of mismatch repair proteins may be caused by epigenetic or genetic factors. Complete profiling is not routinely performed in clinical practice. We sought to explore outcomes of women with mismatch repair deficiency (MMRd) due to epigenetic MLH-1 promoter hypermethylation (MMRd-MLH). We hypothesize that MMRd-MLH correlates with worse clinical outcomes in endometrial cancer. Methods: Under an IRB protocol, we retrospectively identified patients with endometrioid endometrial adenocarcinoma undergoing hysterectomy at our institution from 2016-2020. These patients underwent routine immunohistochemical testing for MMRd, with subsequent genetic testing or methylation studies for loss of MMR proteins. We examined patient data in three cohorts: MMR proficient (MMRp), MMRd-MLH, and MMRd deficiency due to germline mutation (MMRd-G). We excluded patients who did not undergo MMR testing and those who were MMR deficient due to other causes. We examined clinical data via univariate and multivariate tests and Kaplan-Meier survival analyses. Results: We identified 327 patients who met the criteria for review. The majority (243, 74%) were MMRp, 74 (23%) were MMRd-MLH, and ten (3%) were MMRd-G. On univariate analysis, we observed no differences in the history of post-menopausal hormone replacement therapy, family history of cancer, personal history of hypertension or diabetes mellitus, or body mass index. We found that when compared to the other two groups, MMRd-MLH patients were more like to have grade 2-3 tumors (p < 0.01) and LVSI (p < 0.001). We identified statistically significant associations between age at surgery (60, 67, and 60 years, respectively) and depth of invasion (0.41cm, 0.67cm, and 0.18cm). We did not observe significant differences in the stage. We identified that MMRd-MLH was associated with pathologic high-intermediate risk factors leading to increased adjuvant therapy in stage I disease (p=0.04). We observed a 4.1% recurrence rate in MMRp compared to 8.1% in the MMRd-MLH group compared to no recurrences in MMRd-G (p = NS). When comparing MMRp and MMRd-MLH in Kaplan-Meier analyses, we observed a statistical difference in disease-free survival favoring those who were MMRp (p = 0.02). Median survival was not reached. There were no significant differences in overall survival between MMRp and MMRd-MLH. We did not identify independent prognostic factors for recurrence when controlling for age, stage, grade, or MMR status. [Display omitted] Conclusions: MMRd-MLH is associated with LVSI, higher grade, deeper tumor invasion, and a significantly higher rate of adjuvant therapy. We observed patients with MMRd-MLH were more likely to recur despite adjuvant therapy. MMRd-MLH may represent a poor prognostic factor and a target for further adjuvant therapy. [ABSTRACT FROM AUTHOR]

We hypothesize that women with brain metastases from endometrial cancer (EC) will share similar features of histology, initial stage, and time to recurrence. A retrospective chart review was performed with case identification through Natural language processing with Deep6 AI to identify all patients with endometrial cancer and bone metastasis at our institution between 2010 and 2020. Patient demographics, stage, grade, timing of metastasis and other characteristics were recorded. Standard statistical analyses were used to analyze the data. Twelve patients who met study inclusion were identified. The median age at initial diagnoses was 61 years. Two patients (16%) were diagnosed with brain metastasis at initial diagnosis of EC. Patients were equally distributed between stage I, III and IV with 4 patients (33%) in each group. Histology divided between serous (41%) Endometrioid (41%) Dedifferentiated (8%) and Mixed (8%) at diagnosis. Of endometrioid tumors(n=5) all were grade II. Mismatch repair (MMR) status was available for 4 patients (33%) patients and of those 1 was positive for MLH1 Mutation. In those patients who did not have brain metastasis present on initial diagnosis the median time from initial diagnosis to first location of recurrence was 24 months (Range 4-107 months) and to brain metastasis was 41 months (Range 4-140 months). Of those patients who had recurrent disease then progressed to brain metastasis, the median time from initial recurrence to brain metastasis was 25.5 months (Range 4-116 months). Other locations of recurrence included bone, lungs, liver, and mediastinum. Treatment for the brain metastasis varied widely but the most common was radiation which was included in the therapy of 77% of those treated. 22% had surgery which was combined with radiation or other systemic therapy. One patient with leptomeningeal disease was treated with intrathecal methotrexate. [Display omitted] Patients with brain metastasis from endometrial cancer tend to have higher grade and stage tumors at initial diagnosis. They have varying histology, presenting stage, and time to recurrence. Time of progression of initial non-brain recurrence to brain metastasis varies greatly. Further study is required to define patterns and timing of recurrence so treatment and counseling on risks can be optimized. [ABSTRACT FROM AUTHOR]