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Background The Cancer Genome Atlas identified four molecular subgroups of endometrial cancer with survival differences based on whole genome, transcriptomic, and proteomic characterization. Clinically accessible algorithms that reproduce this data are needed. Our aim was to determine if targeted sequencing alone allowed for molecular classification of endometrial cancer. Methods Using a custom-designed 156 gene panel, we analyzed 47 endometrial cancers and matching non-tumor tissue. Variants were annotated for pathogenicity and medical records were reviewed for the clinicopathologic variables. Using molecular characteristics, tumors were classified into four subgroups. Group 1 included patients with > 570 unfiltered somatic variants, > 9 cytosine to adenine nucleotide substitutions per sample, and MSH2, MSH6, MLH1, PMS2. Group 3 included patients with TP53 mutations without mutation in mismatch repair genes. Remaining patients were classified as group 4. Analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, North Carolina, USA). Results Endometrioid endometrial cancers had more candidate variants of potential pathogenic interest (median 6 IQR 4.13 vs. 2 IQR 2.3; p PTEN (82% vs. 15%, p PIK3CA (74% vs. 23%, p TP53 (18% vs. 77%, p POLE mutations, most commonly P286R and V411L. Of the grade 3 endometrioid carcinomas, those with POLE mutations were less likely to have risk factors necessitating adjuvant treatment than those with low tumor mutational burden. Targeted sequencing was unable to assign samples to microsatellite unstable, copy number low, and copy number high subgroups. Conclusions Targeted sequencing can predict the presence of POLE mutations based on the tumor mutational burden. However, targeted sequencing alone is inadequate to classify endometrial cancers into molecular subgroups identified by The Cancer Genome Atlas.

Objective Endometrial cancer survivors are the least physically active of all cancer survivor groups and exhibit up to 70% obesity. While studies suggest lifestyle interventions result in improved health outcomes, recruitment and availability of these programs are limited. The purpose was to evaluate the acceptability and validity of the Fitbit Alta™ physical activity monitor (Fitbit) for socioculturally diverse endometrial cancer survivors. Methods Thirty endometrial cancer survivors were given wrist-worn Fitbits to wear for 30 days. Participants then returned the Fitbits, completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ), Technology Acceptance Questionnaire, and answered qualitative prompts. Correlations between daily Fitbit step counts, demographic factors, body mass index (BMI), and GLTEQ Index, were analyzed using Stata 13.0. Concordance Correlation Coefficient using U statistics was used to examine convergent validity. Results Twenty-five participants completed the study. Mean age was 62 ± 9 years. Mean BMI was 32 ± 9 kg·m −2 . Self-identified race/ethnicity was 36% Hispanic, 36% non-Hispanic white, 16% non-Hispanic black and 12% Asian. Participants wore the Fitbits a median of 93% of possible days. Median daily Fitbit step count was 5325 (IQR: 3761–8753). Mean Technology Acceptance score was 2.8 ± 0.5 out of 4.0. Younger ( p p = 0.99) between step count and GLTEQ Index. Most free responses reflected positive experiences. Conclusions The Fitbits were well accepted in this sample. Self-reported physical activity was not associated with steps recorded. The physical activity data indicate an insufficiently active population.

Obesity confers an overall increased risk for development of endometrial cancer. However there are conflicting reports regarding the effect of obesity on patients' overall and disease specific survival. The purpose of this study was to evaluate the effect of obesity on survival in women with endometrial cancer.After IRB approval, records of women with diagnosis and treatment of endometrial cancer from 1999 to 2016 were abstracted for histopathological, treatment and demographic data. Death was confirmed by query of the Social Security Death Index. Kaplan Meier survival curves and Cox regression modeling was performed with Stata version 14.0.Of 1732 evaluable patients, there were significant differences in age at diagnosis, histology (endometrioid versus non-endometrioid), stage, race, grade, hypertension, hyperlipidemia, diabetes, and treatment between normal weight, overweight, obese, and morbidly obese patients (p 0.01). There was a linear association of younger age at diagnosis with increasing obesity (p 0.01) RObesity is associated with younger age at diagnosis and earlier stage disease. Obesity is associated with improved disease specific survival for stage 3 and 4 non-endometrioid endometrial cancers.

Objectives: Dysbiosis is thought to promote endothelial dysfunction and chronic inflammation, resulting in many chronic human diseases including cancer. This pilot study sought to characterize the cervicovaginal, endometrial and anorectal micro- and mycobiota of post-menopausal women with endometrioid endometrial adenocarcinoma (EAC), uterine serous carcinoma (USC), and controls without cancer. Methods: Post-menopausal patients undergoing hysterectomy for endometrial cancer or non-cancerous disease were enrolled after informed consent. Women were excluded if they reported history of prior cancer, recent urinary or gynecologic infection, antibiotic or probiotic use. Microbial swabs were obtained from the cervicovaginal, the anorectal, and the endometrial cavity after removal of the uterus. DNA was extracted and PCR amplified using barcoded 16SV4 (bacterial) and ITS1 (fungal) primers. Next generation libraries were prepared and sequenced on an Illumina MiSeq 2x300. Sequence reads were processed using our internally developed bioinformatics pipeline and publically available software. Results: Next-generation sequencing of bacterial and fungal DNA revealed substantial differences of cervicovaginal, endometrial and anorectal microbiota in patients with USC (n= 8) compared to those with EAC (n= 13) or benign disease (n= 6). Uterine fungal reads were much higher in patients with USC than EAC (average of 3237 reads versus 938 reads respectively, p = 0.05 Wilcox test). Candida species were reduced, but not eliminated in cervicovaginal samples, and there was a dominance of Malassezia restrica in USC and EAC. A non-significant predominance of Porphyromonas species was noted in USC specimens compared to EAC specimens (p = 0.063). Conclusions: Alpha-diversity of 16S bacterial rRNA and fungal species of the cervicovaginal microbiome was significantly associated with endometrial cancer in our study. USC had a fundamentally different microbiome from control samples and demonstrated a predominance of Porphyromonas species. Further sampling and analysis is needed to confirm these results and to identify rare pathogens. Characterization of microbiota in women with endometrial cancer may help identify risk factors for gynecologic malignancy, and drive investigation regarding preventative and therapeutic intervention. Citation Format: Gregory M. Gressel, Marina Frimer, Christine P. Zolnik, Mykhaylo Usyk, Devin T. Miller, Eirwen M. Miller, D. Y.S. Kuo, Robert D. Burk. Characterization of the cervicovaginal, endometrial and anorectal microbiota and mycobiota of post-menopausal women with endometrioid and serous endometrial cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5143.