Peritumoral adipose tissue promotes lipolysis and white adipocytes browning by paracrine action.

Background: Stromal adipocytes and tumor breast epithelial cells undergo a mutual metabolic adaptation within tumor microenvironment. Therefore, browning and lipolysis occur in cancer associated adipocytes (CAA). However, the paracrine effects of CAA on lipid metabolism and microenvironment remodeling remain poorly understood. Methods: To analyze these changes, we evaluated the effects of factors in conditioned media (CM) derived from explants of human breast adipose tissue from tumor (hATT) or normal (hATN) on morphology, degree of browning, the levels of adiposity, maturity, and lipolytic-related markers in 3T3-L1 white adipocytes by Western blot, indirect immunofluorescence and lipolytic assay. We analyzed subcellular localization of UCP1, perilipin 1 (Plin1), HSL and ATGL in adipocytes incubated with different CM by indirect immunofluorescence. Additionally, we evaluated changes in adipocyte intracellular signal pathways. Results: We found that adipocytes incubated with hATT-CM displayed characteristics that morphologically resembled beige/brown adipocytes with smaller cell size and higher number of small and micro lipid droplets (LDs), with less triglyceride content. Both, hATT-CM and hATN-CM, increased Pref-1, C/EBPß LIP/LAP ratio, PPARγ, and caveolin 1 expression in white adipocytes. UCP1, PGC1α and TOMM20 increased only in adipocytes that were treated with hATT-CM. Also, hATT-CM increased the levels of Plin1 and HSL, while decreased ATGL. hATT-CM modified the subcellular localization of the lipolytic markers, favoring their relative content around micro-LDs and induced Plin1 segregation. Furthermore, the levels of p-HSL, p-ERK and p-AKT increased in white adipocytes after incubation with hATT-CM. Conclusions: In summary, these findings allow us to conclude that adipocytes attached to the tumor could induce white adipocyte browning and increase lipolysis as a means for endocrine/paracrine signaling. Thus, adipocytes from the tumor microenvironment exhibit an activated phenotype that could have been induced not only by secreted soluble factors from tumor cells but also by paracrine action from other adipocytes present in this microenvironment, suggesting a "domino effect".

Minimally invasive surgery versus laparotomy in women with high risk endometrial cancer: A multi-center study performed in Argentina.

Objective: Compare the perioperative outcomes and disease-free survival between minimally invasive and open surgery in women with stage I-II high-risk endometrial cancer. Methods: A retrospective, cohort study was performed involving twenty-four centers from Argentina. Patients with grade 3 endometrioid, serous, clear cell, undifferentiated carcinoma or carcinosarcoma who underwent hysterectomy, bilateral salpingo-oophorectomy, and staging between January 2010-2018 were included. Cox hazard regression analysis and Kaplan-Meier curves evaluated the association of surgical technique with survival. Results: Of 343 eligible patients, 214 (62 %) underwent open surgery and 129 (38 %) underwent laparoscopic surgery. No significant differences were seen between the two groups with respect to greater or equal grade III Clavien-Dindo postoperative complications (11 % in the open surgery group vs 9 % minimally invasive surgery group; P = 0.34) Minimally invasive surgery was not associated with worse disease-free survival at four years (79.14 % [95 % CI 69.42- 86.08] vs 78.80 % [95 % CI 70.61-84.96]), (p = 0.25), even after creating a Cox proportional model (hazard ratio [HR] 1.08 95 % CI 0.63-1.84); (p = 0.76). Conclusion: There was no difference between postoperative complications nor oncologic outcomes comparing minimally invasive and open surgery among patients with high-risk endometrial cancer.

Comparative proteomics of soluble factors secreted by human breast adipose tissue from tumor and normal breast.

Tumor progression depends on the tumor-stroma interaction. In the breast, adipose tissue is the predominant stromal type. We have previously demonstrated that conditioned media (CMs) from explants of human adipose tissue of tumor breasts (hATT) increase proliferation and migration of breast cancer epithelial cells when compared to human adipose tissue from normal breasts (hATN). In this work, we aim to identify specific proteins and molecular/biological pathways associated with the secretion profile of hATT and hATN explants. hATT-CMs and hATN-CMs were separated by SDS-PAGE and analyzed by means of two-dimensional nano-liquid chromatography-mass spectrometry. The data was analyzed using ProteoIQ and FunRich software. In addition, 42 cytokines from hATT-CMs and hATN-CMs were assayed by a protein antibody assay. Compared to hATN-CMs, hATT-CMs showed greater protein diversity. We found that hATT-CMs presented a greater amount of proteins related to complement system activity, metabolism and immune system, as well as proteins involved in a variety of biological processes such as signal transduction and cell communication. Specifically, apolipoprotein AI and AII, complement component 3, and vimentin and desmin were significantly increased in hATT-CMs versus hATN-CMs. Moreover, a multivariate discriminant analysis of the cytokines detected by the array showed that IL-6, MCP-2 and GRO cytokines were sufficient and necessary to differentiate hATT-CMs from hATN-CMs. This analysis also showed that the levels of these three cytokines, taken together, correlated with stage and histological grade of the tumor in the hATT-CMs group, and with body mass index in the hATN-CMs group.

Luminal B. Factor pronóstico y predictivo del Ki67 / Luminal B. Prognostic and predictive factor of Ki67

Introducción El cáncer de mama es una enfermedad heterogénea; tumores con factores pronósticos similares presentan diferente evolución, lo que hace suponer que la diferencia es molecular. El antígeno de proliferación celular Ki67 es un factor clave que representa la actividad mitótica celular. Objetivos Analizar el subtipo Luminal B y el valor del Ki67, evaluando su relación con los factores pronósticos y predictivos clásicos, y determinar su utilidad para subclasificar grupos moleculares en función del mismo. Material y métodos Estudio descriptivo, retrospectivo, analítico observacional. Se revisaron 520 fichas de patología mamaria pertenecientes al Hospital Churruca y al Sanatorio Corporación Médica General San Martín, en el período comprendido entre enero 2010-enero 2015. Fueron analizadas 82 pacientes subtipo Luminal B, con Ki67 elevado. Resultados La mediana de expresión del Ki67 fue de 25,9% y del 34% en las pacientes recaídas. Discusión Se observó relación proporcional del Ki67 con el tamaño tumoral y el grado histológico. Conclusiones El Ki67 debe ser analizado en la práctica diaria por patólogos expertos, a fin de predecir el comportamiento frente a tratamientos adyuvantes de una manera más certera, adecuando la terapéutica a cada paciente.

Introduction Breast cancer is a heterogeneous disease; tumors with similar prognostic factors have different evolution, which suggests that the difference is at the molecular level. The proliferation antigen Ki67 is a key factor that represents the cell mitotic activity. Objectives Analyze Luminal B subtype and the value of Ki67, evaluating its relationship with prognostic and predictive factors conventionally used. Determine its usefulness for subclassified different molecular groups. Matherials and method Observational analytical retrospective study. We reviewed 520 breast cancer files belonging to Churruca Hospital and Sanatorio Corporación Médica General San Martín in the period between January 2010- January 2015. We analyzed 82 patients Luminal B subtype with hight Ki67. Results The median expression of Ki67 was 25.9 % and 34% in patients with relapsed. Discussion We found proportional relationship between the value of Ki67 with tumor size and histologic hight grade. Conclusions The Ki67 must be analyzed in daily practice validated by expert pathologists in late predict behavior towards adjuvant treatments in a more accurate way available, adapting to each patient therapeutic methods.