Endometrial Carcinomas With Subclonal Loss of Mismatch Repair Proteins: A Clinicopathologic and Genomic Study.

Subclonal loss of mismatch repair (MMR) proteins has been described in a small subset of endometrial carcinomas (ECs), but the genomic basis for this phenomenon has received limited attention. Herein, we retrospectively evaluated all ECs with MMR immunohistochemistry (n=285) for subclonal loss, and in those (n=6), performed a detailed clinicopathologic and genomic comparison of the MMR-deficient and MMR-proficient components. Three tumors were FIGO stage IA, and one each stage IB, II, and IIIC2. Patterns of subclonal loss were as follows: (1) 3 FIGO grade 1 endometrioid carcinomas with subclonal MLH1/PMS2, MLH1 promoter hypermethylation, and no MMR gene mutations; (2) POLE -mutated FIGO grade 3 endometrioid carcinoma with subclonal PMS2, and PMS2 and MSH6 mutations limited to the MMR-deficient component; (3) dedifferentiated carcinoma with subclonal MSH2/MSH6, as well as complete loss of MLH1/PMS2, MLH1 promoter hypermethylation, and PMS2 and MSH6 mutations in both components; (4) dedifferentiated carcinoma with subclonal MSH6, and somatic and germline MSH6 mutations in both components, but with a higher allele frequency in MMR-deficient foci. Recurrences occurred in 2 patients, one consisted of the MMR-proficient component from a FIGO 1 endometrioid carcinoma, while the other was from the MSH6 -mutated dedifferentiated endometrioid carcinoma. At the last follow-up (median: 44 mo), 4 patients were alive and disease-free and 2 were alive with disease. In summary, subclonal MMR loss reflects subclonal and often complex genomic and epigenetic alterations, which may have therapeutic implications and therefore must be reported when present. In addition, subclonal loss can occur in both POLE -mutated and Lynch syndrome-associated ECs.

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.

Chemotherapy response score as a prognostic tool in patients with advanced stage endometrial carcinoma treated with neoadjuvant chemotherapy.

BACKGROUND: Chemotherapy response score (CRS) applied to interval debulking specimens quantifies histopathologic response to neoadjuvant chemotherapy in patients with advanced ovarian carcinoma and correlates with progression-free and overall survival. OBJECTIVE: To investigate whether the chemotherapy response score could be applied to interval debulking specimens in patients with advanced endometrial carcinoma and be a prognostic indicator. METHODS: The study included patients with clinical stage III-IV endometrial carcinoma who received neoadjuvant chemotherapy followed by interval debulking surgery. Chemotherapy response scores were assigned to omental and adnexal metastases, and categorized as no/minimal (CRS1), partial (CRS2), and complete/near-complete (CRS3) response to neoadjuvant chemotherapy. Descriptive statistics were used to evaluate baseline characteristics and feasibility of chemotherapy response score assessment. Univariate analyses were used to evaluate associations between the chemotherapy response score, complete cytoreduction, and survival. RESULTS: This study included 40 patients. The median age was 63.5 years, and 31 patients (78%) had stage IV disease. Thirty patients had an omentectomy, 22 patients (73%) had an omental chemotherapy response score assigned. Thirty-nine patients had a bilateral salpingo-oophorectomy, 28 patients (72%) had an adnexal chemotherapy response score assigned. Omental CRS2 and CRS3 were associated with improved progression-free survival (CRS2: HR=0.18, p<0.01; CRS3: HR=0.11, p<0.01) and overall survival (CRS2: HR=0.10, p<0.01; CRS3: HR=0.16, p=0.04). Adnexal CRS2 and CRS3 were associated with improved progression-free survival (CRS2: HR=0.23, p<0.01; CRS3: HR=0.20, p=0.03). Chemotherapy response scores were also associated with an increased likelihood of having a complete cytoreduction. CONCLUSION: Chemotherapy response score can be applied to omental and adnexal metastases in patients with advanced endometrial carcinoma and was associated with survival and complete cytoreduction. The score may be a prognostic indicator and help to guide first-line treatment of patients with endometrial carcinoma.