White adipose tissue (WAT), once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic, heterogenous, and involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control, and host defense 1 . High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition 1 , and alterations in adiposity are associated with insulin resistance, dyslipidemia, and type 2 diabetes (T2D) 2 . Here, we provide detailed cellular atlases of human and murine subcutaneous and visceral white fat at single cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease, and we provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits, and cell types in the function of WAT across species, depots, and nutritional conditions.

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.

Objectives To assess clinicopathologic outcomes between two nodal assessment approaches in patients with endometrioid endometrial carcinoma and limited myoinvasion. Methods Patients with endometrial cancer at two institutions were reviewed. At one institution, a complete pelvic and para-aortic lymphadenectomy to the renal veins was performed in select cases deemed at risk for nodal metastasis due to grade 3 cancer and/or primary tumor diameter >2 cm (LND cohort). This is a historic approach at this institution. At the other institution, a sentinel lymph node mapping algorithm was used per institutional protocol (SLN cohort). Low risk was defined as endometrioid adenocarcinoma with myometrial invasion <50%. Macrometastasis, micrometastasis, and isolated tumor cells were all considered node-positive. Results Of 1135 cases identified, 642 (57%) were managed with an SLN approach and 493 (43%) with an LND approach. Pelvic nodes (PLNs) were removed in 93% and 58% of patients, respectively (P<0.001); para-aortic nodes (PANs) were removed in 14.5% and 50% of patients, respectively (P<0.001). Median number of PLNs removed was 6 and 34, respectively; median number of PANs removed was 5 and 16, respectively (both P<0.001). Metastasis to PLNs was detected in 5.1% and 2.6% of patients, respectively (P=0.03), and to PANs in 0.8% and 1.0%, respectively (P=0.75). The 3-year disease-free survival rates were 94.9% (95%CI, 92.4–97.5) and 96.8% (95%CI, 95.2–98.5), respectively. Conclusions Our findings support the use of either strategy for endometrial cancer staging, with no apparent detriment to the SLN algorithm. The clinical significance of disease detected on ultrastaging and the role of adjuvant therapy is yet to be determined.

Purpose To characterize treatment patterns and oncologic outcomes in patients with low-volume lymph node metastasis (isolated tumor cells [ITCs] and micrometastasis [MM]) discovered during sentinel node (SLN) mapping for endometrial carcinoma. Methods We identified endometrial cancer cases treated surgically from 9/2005-4/2013 in which SLN mapping was performed. MM was defined as tumor within a lymph node measuring >0.2mm but <2.0mm. ITCs were those measuring ≤0.2mm. Results Eight hundred forty-four patients met inclusion criteria. Median age was 61 (range, 30-90). Histology was as follows: endometrioid, 724 (85.8%); serous, 104 (12.3%); and clear cell, 16 (1.9%). Median number of lymph nodes resected was 6 (range, 0-60); median number of SLNs was 2 (range, 0-15). Seven hundred fifty-three patients (89.2%) were node negative, 23 (2.7%) had ITCs only, 21 (2.5%) had MM only, and 47 (5.6%) had macrometastasis. Adjuvant chemotherapy was given to 106 (14%) of 753 node-negative patients, 19 (83%) of 23 patients with ITCs, 17 (81%) of 21 patients with MM, and 42 (89%) of 47 with macrometastasis. Median follow-up was 26 months (range, 0-108). Three-year recurrence-free survival was as follows: node-negative patients, 90% (± 1.5); ITCs only, 86% (± 9.4); MM only, 86% (± 9.7); and macrometastasis, 71% (± 7.2), (p<0.001). Conclusion Patients with ITCs and MM frequently received adjuvant chemotherapy, and had improved oncologic outcomes in comparison to those with macrometastasis to the lymph nodes. Further prospective study is needed to determine optimal post-resection management in patients with ITCs or MM alone.

White adipose tissue (WAT), once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic, heterogenous, and involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control, and host defense1. High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia, and type 2 diabetes (T2D)2. Here, we provide detailed cellular atlases of human and murine subcutaneous and visceral white fat at single cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease, and we provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits, and cell types in the function of WAT across species, depots, and nutritional conditions.

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Use of an SLN algorithm in deeply invasive EEC does not impair oncologic outcomes. Survival is excellent in node-negative cases, irrespective of assessment method. Adjuvant chemotherapy in node-negative patients does not appear to impact outcome.

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