Characterization of the impact of obesity on the morphological, metabolic, molecular, and inflammatory profile of adipose tissue in patients with endometrial cancer.
endometrial cancer; obesity; inflamation; adipose tissue; molecular profile ; WES
Introduction Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries, with a progressive increase in incidence associated with obesity. Obesity promotes hormonal, metabolic, and inflammatory changes that favor endometrial proliferation and carcinogenesis. Adipose tissue, in addition to serving as an extragonadal source of estrogen, functions as an active endocrine and immunometabolic organ that secretes adipokines and pro-inflammatory cytokines that modulate the tumor microenvironment. Inflammation of white adipose tissue (WAT), characterized by the presence of crown-like structures (CLS), reflects local metabolic dysfunction and may influence molecular heterogeneity and prognosis in EC. Objectives: To investigate the relationship between obesity, adipose tissue inflammation, and molecular profile in endometrial cancer, correlating clinical, histopathological, immunological, and genomic features. Methods: This is an observational, retrospective, and exploratory study including patients with histopathologically confirmed endometrial cancer who underwent surgery at the University Hospital of Brasília between 2013 and 2023. Tumor and peritumoral adipose tissue samples were histologically reviewed by experienced pathologists to ensure adequate morphological preservation. Tumor tissue underwent immunohistochemical (IHC) characterization for preliminary molecular classification. Whole-exome sequencing (WES) will be conducted in a subsequent phase to identify pathogenic variants and refine stratification according to TCGA molecular subgroups. Peritumoral adipose tissue was subjected to morphometric analysis and subsequently to inflammatory evaluation, including assessment of inflammatory infiltrates and crown-like structures. Partial Results: A total of 58 patients were included, with a median age of 65 years and a mean body mass index (BMI) of 30.25 kg/m². Most patients were overweight or obese (89.7%). Endometrioid histology was the most frequent subtype (65.5%). Among cases with available molecular profiling, the p53-aberrant subtype predominated (25.9%), followed by MMR-deficient (22.4%) and NSMP (37.9%). In the morphometric analysis of peritumoral adipose tissue (n = 45), the median adipocyte diameter was 59.4 µm (P25: 54.4; P75: 64.3), with a median interquartile range (IQR) of 19.6 µm and a median proportion of large adipocytes of 38.8%. No significant associations were observed between morphometric parameters and BMI, molecular subtypes, or recurrence Perspectives: The following stages include morphometric quantification of adipose tissue and identification of CLS, immunophenotypic characterization of macrophages, and integration of genomic data from WES. The combined analysis of these parameters is expected to clarify how adipose tissue inflammation and systemic metabolic status influence the tumor microenvironment and molecular subtypes of EC. These findings may contribute to improving prognostic stratification and developing personalized therapeutic strategies.Palavras chaves em português: câncer de endométrio; obesidade; inflamação; tecido adiposo; perfil molecular; WES