We aim to examine the expression of HLA-G, an immunoregulatory protein, in Endometrial Hyperplasia (EH) and its association with risk of endometrial cancer occurrence and progression.
This will be a retrospective single institutional study. 40 patients with pathological diagnosis of complex atypical endometrial hyperplasia, who underwent subsequent hysterectomy or repeated biopsy, will be identified and evaluated for the risk of endometrial carcinoma occurrence. Immunohistochemical stains for HLA-G expression will be performed on the 40 identified biopsies positive for endometrial hyperplasia. The expression degree will be correlated with the presence of cancer in follow up tissue.
HLA-G is an HLA class I molecule, whose primary function is to protect the fetus from destruction by the mother¿s immune system, playing a role in maternal-fetal tolerance (1-3). Thus, HLA-G is one of the proteins whose physiological immune function is exerted primarily towards foreign tissues. Under normal physiological conditions, HLA-G is hardly expressed by adult tissues. By contrast, most tumors neoexpress HLA-G at different stages of their evolution, either on their cell surface or released as soluble forms. In vitro and in vivo studies of the function of HLA-G revealed a broad immunoregulating function that affects both innate and adaptive immune responses. HLA-G also induces Treg cells and myeloid suppressive cells. Thus, HLA-G is able to inhibit several actors in antitumor responses and, in contrast to both CTLA-4 and PD-1, of blocking all stages of antitumor response, from APC activation and effector priming, to the function of fully activated CTLs or NK cells. In cancer, HLA-G is expressed on tumor cells and tumor-infiltrating cells. HLA-G expression is associated with higher tumor grade and worse prognosis (3). HLA-G plays a key role in the induction of immune tolerance and constitutes a novel immune escape mechanism of tumor cells. However, the therapeutic role of HLA-G peptide-based immunotherapy requires further investigation (4,5). Tumor initiation, promotion, progression, metastasis, and clinical findings depend on the response of the host immune system to the tumor cell, as mediated by the inflammatory and coagulation systems. Endometrial cancer is usually due to unbalanced estrogen and develops on a background of various degrees of hyperplasia(6). Inflammatory cells and their changes have been studied in precursor lesions and endometrial cancer, as in many other cancers(7).
Endometrial hyperplasia (EH) occurs when endometrial cells exposed to the estrogen for a long time and it is known as one of the most important risk factor of endometrial cancer(8,9). Typically, hyperplasia with atypia is treated by means of hysterectomy. In patients with atypical endometrial hyperplasia, the detection of endometrial cancer risk before hysterectomy can decrease the risk of overtreatment especially in young women who wish to preserve fertility(10,11). So it is important to stratify the risk of progression to cancer in endometrial hyperplasia. In order to avoid the consequences of over- and under-treatment of endometrial hyperplasia, diagnostic accuracy and progression risk assessment must be improved.The research will innovatively explore the role of the HLA-G in the carcinogenesis of EH. if this hypothesis were verified, it could mean considering HLA-G as a prognostic factor for the management of EH and also as a basis for future immunotherapies
References
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