Human Leukocyte Antigen-E Is Expressed By The Eutopic And Ectopic Endometrium Of Adenomyosis

Adenomyosis is a common but complex gynecological syndrome of unknown pathogenesis that preferentially affects parous women between the ages of 35 and 50 years. The disease is characterized by ectopic growth of endometrial tissues within the myometrium, surrounded by the hypertrophic and hyperplastic myometrium. The presenting symptoms include a soft and diffusely enlarged uterus, menorrhagia,dysmenorrhea, and subfertility .though adenomyosis differs somewhat from endometriosis in its risk factor profile ,the two nonetheless share an uncanny similarity in definition, estrogen dependence,symptomatology, and many documented molecular aberrations. In addition, the two often occur concurrently. These similarities, of course, may not necessarily imply an identical pathogenesis, yet they are too numerous to ignore. Only in recent years, with the introduction of new imaging techniques and molecular diagnostic tools, It is possible that some culprits that have been identified to be involved in the pathogenesis of endometriosis may also be involved in adenomyosis.Thus, the only difference between adenomyosis and endometriosis is the site of endometriotic tissues, that is,within or outside the uterus. It has become clear that adenomyosis and endometriosis may represent different phenotypes of a more profound disorder characterized by impaired cellular responses to ovarian sex steroids throughout the reproductive tract. Although advances in our understanding of the cross-talk between steroid hormone receptors and cell-surface signalling pathways are of particular relevance to the pathogenesis of endometriosis, the search for a molecular definition of this syndrome has barely started.It is well known that endometriosis is frequently associated with various autoimmune phenomena.in analogy to adenomyosisi ,a series of immune responses is activated,including changes in both cellular and humoral immunity.Recently,it was found that leukocyte antigen-E (HLA-E) is expressed by the glandular epithelium of peritoneal endometriosis. Yet the literature does not include similar reports on adenomyosis. HLA-E is a nonclassical major histocompatibility complex class I antigen(HLA-Ib) that was first found to be restrictively expressed by the fetal–maternal interface on the extravillous cytotrophoblast. The presence of HLA-E at this immunologically privileged site was proposed to serve as protection for the fetus from maternal allorecognition as the fetus and the placenta are semi-allogenic to the mother. in more details, its ability to suppress immune cell functions, such as natural killer cell–mediated and cytotoxic T lymphocyte–mediated cytolysis and T-cell proliferative response. However, recent studies have shown that HLA-E expression has been detected in several human cancers,except in trophoblast, including melanoma,renal cell carcinoma, breast carcinoma and choriocarcinoma. The aberrant expression of HLA-E antigens by tumor cells has been suggested to be part of the set of strategies that they use to escape from the host's immunosurveillance, in analogy to the role of HLA-E antigens in the escape of trophoblasts from maternal allorecognition.Therefore, it has been postulated that expression of HLA-E by endometriosis and adenomyosis lesions may explain their ability to persist within the peritoneal cavity and myometrium without being eliminated by the host's immune system. Thus, we designed this study to demonstrate whether adenomyosis patients also express HLA-E in the ectopic and/or eutopic endometrium, just as the endometriosis patients do.Materials and MethodsThe study subjects enrolled between December 2008 and October 2009 at the Department of Gynecology. Adenomyosis and leimyoma were confirmed histologically. Sixty-two women with active adenomyosis lesions were assigned to the adenomyosis group.twenty control subjects were undergoing hysterectomy for myoma of the uterus and had no visible evidence found of other pathology. Using SP immunonhistochemical technique ,we examined the expression of HLA-E in 20 normal endometrium of uterine leiomyoma ,62 cases of adenomyosis in eutopic and ectopic lesions(including ectopic endometrium and surrounding tissue).Women receiving hormonal treatment including oral contraceptives during the 3 months before operation,as well as those with endocrine, immunologic, or neoplastic or other chronic diseases or those suspected of having complications of pelvic inflammatory disease, were excluded from the analysis. The women with adenomyosis were similar to those with myoma, in age (43.6 +4.1y for the former vs.45.6±3.6 y for the latter) . In the adenomyosis group, adenomyotic foci were limited to the half Shallow (<1/2) and deep (≥1/2) layers of the myometrium in 36 and 26 cases, respectively.Besides,the adenomyosis group were divided into proliferative and secretory phase groups according to pathological results,42 and 20 cases respectively .In addition, the number of adenomyotic foci, the invasion depth, the ratio between the foci depth and the whole muscular wall depth, and the menstrual cycle of all patients were calculated and recorded. The average score from each of the slide was calculated and expressed as mean+SD. T- test was performed to compare scores from examination of ectopic and eutopic endometrium. P value of <0.05 was considered significant. The statistical software SPSS for Windows (version 13.0; SPSS) was used to perform the statistical analysis.ResultThe results showed that, patients with adenomyosis ,eutopic endometrium (A value: 14757.73±4845.37) and the endometriotic lesion (A value: 17332.55±4243.16) were high expression of HLA-E.Respectively, to compared with the control group (A value: 11373.40±3115.72), the difference was significantly (P <0.05). Ectopic lesions compared with eutopic endometrium, the difference was not statistically significant (P> 0.05), A good correlation was found between HLA-E expression in ectopic and eutopic endometrium in patients with adenomyosis,both in glands and in stroma. Further grouping, between cases of proliferative and secretory the expression of HLA-E, the difference was not statistically significant (P> 0.05), more shallow and deep groups the expression of HLA-E, the difference was not statistically significant ( P> 0.05), There is only one case that belongs to the confine adenomyosis.so this factor can not be matched with.Conclusion1. High expression of HLA-E may be involved in the pathogenesis of adenomyosis.2.The glandular and stromal HLA-E expression in both eutopic and ectopic endometrial tissue did not differ according to grade or menstrual cycle and did not correlate with depth of myometrium infiltration, or ratio between the foci depth and the whole muscular wall depth.3. Improving the immune status of patients ,that provide a new idea for the clinical treatment of adenomyosis.In summary, in adenomyosis. ectopic and eutopic endometrial cells were induced to express the HLA-E antigene highly so as to winning a little tide,and this result led us to suppose that HLA-E may play a role in the process of endometrial cell escape from host immune surveillance.This finding provides some new experimental data on the immune tolerance of adenomyosis and may be helpful for developing new strategies to fight this complex disease. The experiment itself can be sure of the immune system abnormalities involved in the occurrence of adenomyosis, but it is unclear whether this abnormality is an independent risk factor.