SUN-133 Intratumoral Expression of Steroid Receptors, CD68+ Macrophages and Mdm2 in Different Molecular-Biological Types of Endometrial Cancer

Abstract

Background and aims: In Risk Classifier for Endometrial Cancer/EC (ProMisE) 4 molecular biological types of this tumor are described recently [1,2,3] and need an additional research, including evaluation of hormone-associated characteristics of both tumor tissue and patients [4]. Aim of the work was a study of estrogen (ER) and progesterone (PR) receptors in comparison with CD68+ macrophage infiltration (which promotes the invasion of tumor cells into the myometrium [5]) and expression of MDM2 protein, a negative regulator of p53 [6], in EC types presented in the ProMisE classification. Materials and methods: The tumor tissue of 218 EC patients included in the study (mean age 60.6 years) was assigned according to the data of genetic and immunohistochemical analysis to the types of carcinomas with gene POLE mutations, deficiency of mismatch repair proteins (MMR-D), expression (positive or diffuse) of p53 oncoprotein and to the type without characteristic molecular profile, WCMP. Immunohistochemistry was used also for evaluation of ER (Ventana antibodies, clone SP1) and PR (Ventana antibodies, clone 1E2) according to Allred, MDM2 (antibodies ABCAM, dilution 1:200) and macrophage marker CD68 (DAKO antibodies, clone CD8/144B). Results: According to the averaged data, the highest expression of ER and PR was found in EC types MMR-D and WCMP, and the lowest, respectively, in types POLE and p53+. Most often, positive expression of MDM2 (in 93.2% and 96.9% of studied cases) was detected respectively in MMR-D and p53+ type of EC, indicating, therefore, a positive relationship between MDM2 and the presence of steroid receptors in the first of these types (MMR-D) and negative - in the second of them (p53+). Expression of CD68+ macrophages demonstrated (contrary to the EC types POLE and p53+) a tendency to the lower values in types MMR-D and WCMP (128.0 ± 8.1 and 113.5 ± 6.3 cond.un.), i.e. in tumors with potential sensitivity to estrogen. Conclusions: The results indicate the importance of taking into account of both - the molecular biological type of the EC as well as the role of microenvironment of tumor cells, including the colonization of the neoplasm’ tissue by macrophages (and possibly lymphocytes) and the features of hormonal signal transmission in it. For further analysis, it is desirable to consider also the EC histotype, as one of the factors underlying various prognostic groups of this tumor [7].