Investigator
University Of Chicago
A Proteogenomic View of Synchronous Endometrioid Endometrial and Ovarian Cancer
Abstract Purpose: Increasing genomics-based evidence suggests that synchronous endometrial and ovarian cancer (SEOC) represents clonally related primary and metastatic tumors. A systematic analysis of the global protein landscape of SEOCs, heretofore lacking, could reveal functional and disease-specific consequences of known genetic alterations, the directionality of metastasis, and accurate histologic markers to distinguish SEOCs from single-site tumors. Experimental Design: We performed a systematic proteogenomic analysis of 29 patients diagnosed with SEOC at three international gynecologic oncology treatment centers (Chicago, Vancouver, and Tübingen). For direct comparison with single-site tumors, we included 9 patients with single-site endometrioid ovarian and 26 patients with single-site endometrioid endometrial cancer (EEC). For all 64 patients, we performed sequencing of a 275-gene cancer panel combined with compartment-resolved mass spectrometry–based proteomics of consecutive tissue sections to compare global (6,000+ proteins), tumor, and stromal proteomes. Results: DNA-based panel sequencing confirmed that most SEOCs are clonally related. Global proteome profiling uncovered pronounced differences between SEOCs and single tumors and underscored the importance of the stromal proteome in defining and identifying SEOCs. We identified molecularly unique SEOC stromal proteomes, which were globally more related to single endometrial cancers. We finally derived a proteomic predictor distinguishing SEOCs from single-site ovarian and uterine tumors. Conclusions: The integrated proteogenomic data show that SEOCs are distinguishable from endometrioid endometrial or endometrioid ovarian cancer. Based on their proteogenomic similarity to EECs, we conclude that most SEOCs represent primary EECs that have metastasized to the ovary.
Resilience in the Face of Pandemic: The Impact of COVID-19 on the Psychologic Morbidity and Health-Related Quality of Life Among Women With Ovarian Cancer
PURPOSE: The COVID-19 pandemic has created new challenges for ovarian cancer survivors. This study aims to evaluate the psychologic morbidity and alterations in medical care caused by the pandemic. METHODS: Advanced-stage ovarian cancer survivors at our institution were contacted for participation in a cross-sectional telephone-based quantitative survey study assessing pandemic-related psychologic morbidity. Psychologic domains using validated measures were explored: health-related quality of life (HRQOL; functional assessment of cancer therapy [FACT-G7]), anxiety (generalized anxiety disorder-7 [GAD7]), depression (Patient Health Questionnarie-2 [PHQ2]), global health Patient-Reported Outcomes Measurement Information System - Global Physical Health/Global Mental Health (PROMIS-GMH/GPH), resilience (brief resilience scale), and loneliness (English Longitudinal Study on Aging). Novel COVID-19 pandemic questions were drawn from a larger survey developed in our department. RESULTS: Fifty-nine percent (61 of 104) of contacted patients completed the survey. One quarter of respondents had high resilience, with only 10% reporting low resilience. Only one patient screened positive for depression, and two for anxiety. Increased loneliness was reported by 43% of respondents. Patients' overall HRQOL was good (median = 21; range = 6-28). Few patients experienced treatment delays, with only four experiencing chemotherapy interruption and two reporting surgical delays. Multiple regression analyses revealed that high FACT-G7 HRQOL was predicted by age > 65 years, high self-reported mental health, high resilience, and being off chemotherapy. Lower COVID-19 concern was predicted by recurrent cancer and high resilience. CONCLUSION: Despite the far-reaching impact of the COVID-19 pandemic, ovarian cancer survivors' HRQOL has been maintained. Older age, high resilience, high mental health, and being off chemotherapy predicted better HRQOL. Ovarian cancer survivors remain resilient in the face of the pandemic, and the support of clinicians to preserve this invaluable personal resource is critical for well-being.
