Human leukocyte antigen, isotype DR (HLA-DR) expression in the normal endometrium and in endometrial pathology

Abstract

BACKGROUND: Human leukocyte antigen, isotype DR (HLA-DR) expression is associated with inflammatory and autoimmune diseases. It is also found on the surface of tumor cells. The role of HLA-DR in endometrial pathology has not been sufficiently studied.

AIM: The aim of this study was to determine HLA-DR expression features in the endometrium under normal and pathological conditions.

MATERIALS AND METHODS: We performed immunohistochemical examination of endometrial biopsy specimens, namely, 18 cases of endometrioid carcinomas, 139 cases of chronic endometritis, and 37 cases of endometrial polyps. The control group included 50 cases of the endometrium without pathology. Positive HLA-DR expression was detected as brown staining of varying intensity of immune cells of the cytogenic stroma, as well as the cytoplasm and membranes of endometrial epithelial cells. The average number of positively stained stromal cells in ten visual fields was counted. HLA-DR expression in the cytoplasm and on the membrane of endometrial epithelial cells was assessed semi-quantitatively as weak (low) (with staining up to 50% of the glands) or pronounced (high) (with staining more than 50% of the glands).

RESULTS: HLA-DRim expression was detected on immune cells of the cytogenic stroma of the endometrium in all of the study groups. HLA-DR expression in the endometrial epithelium was characterized by two main immunophenotypes — negative and positive. Negative HLA-DR expression was found in 55.6% of endometrial cancer cases, in 25.2% of chronic endometritis cases, in 27.7% of endometrial polyp cases, and in all cases of the normal endometrium. The positive HLA-DR (high) immunophenotype was found in 21.6% of chronic endometritis cases, in 28.6% of endometrial polyp cases, and in 16.7% of endometrial cancer cases. Pronounced HLA-DR expression in the epithelium was associated with a high HLA-DR level in the cytogenic stroma and a significantly frequent detection of HLA-DR+ lymphoid follicles in endometrial cancer. The positive HLA-DR (low) immunophenotype was established in 51.8% of chronic endometritis cases and in 27.8% of endometrial polyp cases, and in 27.7% of endometrial cancer cases, and was associated with low HLA-DR levels in the stroma.

CONCLUSIONS: The revealed heterogeneity of HLA-DR expression in chronic inflammation and endometrial cancer allows for distinguishing two main immunophenotypes of endometrial cancer, namely, with negative and positive HLA-DR expression. HLA-DR may be an early predictor of adverse background endometrium and endometrial cancer. The positive HLA-DR immunophenotype of endometrial cancer probably indicates a specific mechanism of carcinogenesis associated with chronic inflammation and requires further comprehensive clinical, morphological and molecular genetic research.

Keywords

endometrial cancer / endometrial polyps / chronic endometritis / human leukocyte antigen, isotype DR / HLA-DR / early diagnosis

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