MON-309 Intratumoral Proliferation and Proinflammatory Macrophages in Obese and Non-Obese Patients with Different Molecular-Biological Types of Endometrial Cancer

Abstract

Background and aims: Endometrial cancer (EC) is characterized in times of modern obesity epidemic by the rapid incidence increase and the recent update of the molecular-biological classification, which now distinguishes not two, as before, but four types of this tumor (Kandoth et al., 2013; Talhouk et al., 2017; Berstein et al., 2017) that need to be comprehensively studied. The objective of this work was to compare the proliferative potential of a tumor tissue (Ki67 index) and compare it with the expression of proinflammatory CD68-macrophages in obese and non-obese patients with different types of EC according to the PROMISE classification. Materials and methods: In all predominantly postmenopausal 216 treatment naive EC patients included in the study, the body mass index (BMI) was estimated due to which the females were divided into subgroups with BMI ≥30.0 and <30.0. According to genetic (high-resolution melting and sequencing) and immunohistochemical (DACO antibodies) analysis, endometrial carcinomas were classified in accordance with recommendations (Talhouk et al, 2017) into types with POLE gene mutations, defect of mismatch repair proteins (MMR-D), expression (positive or diffuse) of p53 oncoprotein and variant without characteristic molecular profile, WCMP. Immunohistochemistry was also used to evaluate the expression of Ki67 (DBS antibodies, clone SP6) and CD68 (DAKO antibodies, clone CD8/144B). Results: Obesity was more common in patients with a WCMP tumor type and, especially, in MMR-D group (BMI ratio ≥30.0/<30.0, respectively, 1.62 and 2.32). The highest Ki67 index values were detected with positive (59.3 ± 3.8%) and a combination of positive and diffuse (50.5 ± 3.7%) p53 expression, and the lowest (27.6 ± 1.7%) in the WCMP group. In all EC types (except for cases with p53+), Ki67 expression was lower at BMI ≥30.0, which was confirmed within this subgroup by negative Spearman correlation of Ki67 level with BMI value. CD68 expression showed a downward trend in the MMR-D and WCMP types (124.4 ± 7.8 and 115.0 ± 5.9 cond.un.) and a tendency to positive correlation with Ki67 in obese women belonging to the POLE and p53 groups. Conclusions: The findings suggest that the level of such important prognostic tumor markers as Ki67 and CD68 (Soeda et al., 2008) is characterized by a relationship with the presence/absence of obesity as well as with EC molecular-biological type, that expands target range for preventive and therapeutic interventions. Acknowledgement to grant 18-015-00026