OBJECTIVETo investigate the expression of the anti-oncogene ARHI in the endometriotic tissue and explore its clinical significance.

METHODSA semiquantitative analysis of the expression of ARHI mRNA and protein in the ectopic and eutopic endometrium of women with endometriosis was conducted using RT-PCR and Western blotting in comparison with that in the endometrium of women without endometriosis. Immunohistochemistry and in situ hybridization were performed for semi qualitative analysis and localization of ARHI expression.

RESULTSThe expression levels of ARHI mRNA and protein differed significantly between the groups. ARHI was expressed at significantly higher levels in ectopic endometrium than in eutopic and normal endometrium (P<0.005), but showed no significant difference between the latter two tissues (Pgt;0.05). The positivity rate ARHI DNA was 97.3% in the endometrium of women without endometriosis, 100% in the ectopic endometrium and 93.8% in the eutopic endometrium of women with endometriosis. immunohistochemistry showed an ARHI positivity of 93.2% in the endometrium of women without endometriosis, 100% in the ectopic endometrium and 92.3% in the eutopic endometrium of women with endometriosis. The expression patterns of ARHI DNA and protein were consistent. Immunohistochemistry in 5 cases of malignant endometriosis showed negative ARHI expression in 4 cases and weak positivity in 1 case.

CONCLUSIONARHI expressions are present in the endometrium and up-regulated in ectopic endometrium, whereas in the ectopic endometrium of patients with malignant endometriosis its expression is often negative, suggesting a role of ARHI in infertility and tumorigenesis of endometriosis.

Adult ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Genes, Tumor Suppressor ; Humans ; RNA, Messenger ; genetics ; rho GTP-Binding Proteins ; metabolism

OBJECTIVETo detect the expression of fragile histidine triad in endometriosis and investigate the pathogenesis of endometriosis.

METHODSimmunohistochemistry was used to examine the expression of Fhit in the eutopic and ectopic endometria of 58 patients with endometriosis and in the endometria in 15 patients with hysteromyoma.

RESULTSThe intensity of Fhit expression decreased in the order of normal endometrium, eutopic endometrium in endometriosis group, and ectopic endometrium. In patients with endometriosis, Fhit expression in the eutopic and ectopic endometria in proliferative phase showed no significant difference from that in secretory phase (P>0.05). Fhit expression in the ectopic endometrium showed significant difference between different r-AFS stages. MOD of ectopic endometrium in stages I-II was significantly higher than that in stages III-IV (P<0.05), but Fhit expression in the eutopic endometrium showed no significant difference (P>0.05). MOD of ovarian endometriosis showed no difference with that of adenomyosis.

CONCLUSIONSFhit may play an important role in the development of endometriosis.

Acid Anhydride Hydrolases ; metabolism ; Adult ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Proteins ; metabolism

At present, endometriosis remains a worldwide health burden, with the main symptoms of dysmenorrhea, chronic pelvic pain, and infertility, markedly reducing the quality of life (de Ziegler et al., 2010). Although there is no proof that the disease is associated with high mortality, this disorder can significantly contribute to the deterioration of women's general well-being (McPeak et al., 2018). The main current treatment for endometriosis is surgery to remove endometriotic lesions; however, the recurrence rate following surgical treatment is as high as 21.5% at two years and 40.0%‍-‍50.0% at five years post-surgery (Koga et al., 2015). To prevent recurrence, adjuvant treatment with drugs after surgery is recommended to prolong relapse-free intervals. However, it is inconvenient for patients to continuously use such medications in terms of adverse effects and cost (Turk, 2002).
Endometriosis/pathology* ; Endometrium/pathology* ; Female ; Humans ; Ki-67 Antigen/metabolism* ; Quality of Life ; Recurrence ; Telomerase/metabolism* ; Up-Regulation

Corded and hyalinized endometrioid carcinoma (CHEC) is a morphologic variant of endo-metrioid adenocarcinoma. The tumor exhibits a biphasic appearance with areas of traditional low-grade adenocarcinoma merging directly with areas of diffuse growth composed of epithelioid or spindled tumor cells forming cords, small clusters, or dispersed single cells. It is crucial to distinguish CHEC from its morphological mimics, such as malignant mixed mullerian tumor (MMMT), because CHECs are usually low stage, and are associated with a good post-hysterectomy prognosis in most cases while the latter portends a poor prognosis. The patient reported in this article was a 54-year-old woman who presented with postmenopausal vaginal bleeding for 2 months. The ultrasound image showed a thickened uneven echo endometrium of approximately 12.2 mm and a detectable blood flow signal. Magnetic resonance imaging revealed an abnormal endometrial signal, considered endometrial carcinoma (Stage Ⅰ B). On hysterectomy specimen, there was an exophytic mass in the uterine cavity with myometrium infiltrating. Microscopically, most component of the tumor was well to moderately differentiated endometrioid carcinoma. Some oval and spindle stromal cells proliferated on the superficial surface of the tumor with a bundle or sheet like growth pattern. In the endometrial curettage specimen, the proliferation of these stromal cells was more obvious, and some of the surrounding stroma was hyalinized and chondromyxoid, which made the stromal cells form a cord-like arrangement. Immunostains were done and both the endometrioid carcinoma and the proliferating stroma cells showed loss of expression of DNA mismatch repair protein MLH1/PMS2 and wild-type p53 protein. Molecular testing demonstrated that this patient had a microsatellite unstable (MSI) endometrial carcinoma. The patient was followed up for 6 months, and there was no recurrence. We diagnosed this case as CHEC, a variant of endometrioid carcinoma, although this case did not show specific β-catenin nuclear expression that was reported in previous researches. The striking low-grade biphasic appearance without TP53 mutation confirmed by immunohistochemistry and molecular testing supported the diagnosis of CHEC. This special morphology, which is usually distributed in the superficial part of the tumor, may result in differences between curettage and surgical specimens. Recent studies have documented an aggressive clinical course in a significant proportion of cases. More cases are needed to establish the clinical behaviors, pathologic features, and molecular profiles of CHECs. Recognition of the relevant characteristics is the prerequisite for pathologists to make correct diagnoses and acquire comprehensive interpretation.
Female ; Humans ; Middle Aged ; Carcinoma, Endometrioid/surgery* ; Endometrial Neoplasms/pathology* ; Endometrium/metabolism* ; Adenocarcinoma/pathology* ; Stromal Cells/pathology*

The expression patterns of CD44s and CD44v6 were immunohistochemically compared with those of normal, hyperplastic and malignant endometrium. In normal endometria (n=37), endometrioses (n=46) and adenomyoses (n=20), the surface and glandular epithelial cells were negative for CD44s and CD44v6 in a proliferative pattern and positive in a secretory pattern, whereas the stroma was only positive for CD44s in both proliferative and secretory patterns. The endometrial hyperplasia (4 simple and 9 complex) had the identical patterns with normal proliferative phase of endometrium. Only one case showing complex hyperplasia with atypia was focally positive for CD44s and CD44v6 in glandular epithelia. CD44s and CD44v6 were positive in all endometrial adenocarcinomas (13), except one CD44s-negative case. In summary, the expressions of CD44s and CD44v6 in endometriosis and adenomyosis recapitulated those of normal cyclic endometrium. The expression patterns in endometrial hyperplasia were similar to those in normal proliferative endometrium, whereas the endometrial adenocarcinoma showed abnormal expressions for CD44s and CD44v6. Thus it was considered that the ectopic endometrium in endometriosis and adenomyosis was not aberrant as in endometrial carcinoma on the aspects of immunohistochemical expressions of CD44s and CD44v6.
Adenocarcinoma/*metabolism/pathology ; Antigens, CD44/*metabolism ; Comparative Study ; Endometrial Hyperplasia/*metabolism/pathology ; Endometrial Neoplasms/*metabolism/pathology ; Endometriosis/*metabolism/pathology ; Endometrium/metabolism/pathology ; Female ; Glycoproteins/*metabolism ; Human ; Immunoenzyme Techniques ; Immunohistochemistry ; Ovarian Diseases/*metabolism/pathology ; Staining and Labeling/methods

OBJECTIVE: To examine the expression of G protein-coupled estrogen receptor (GPER) and Gankyrin in ovarian endometriosis (OEM) and to evaluate its clinicopathological significance.
 METHODS: Immunohistochemistry was conducted to determine the expression and distribution of GPER and Gankyrin in matched ectopic and eutopic endometrium of OEM and the normal endometrium. The association of these two proteins with the stages of OEM was also investigated.
 RESULTS: The positive rate for GPER protein in paired ectopic and eutopic endometrium of OEM and the normal endometrium were 63.6%, 51.5% and 21.2%, respectively. There was significant difference in matched ectopic and eutopic endometrium from OEM compared with the control endometrium (P<0.0125). No statistical significance was found between ectopic and eutopic endometrium from OEM (P>0.0125). The positive rate for Gankyrin protein were 69.7%, 36.4% and 9.1%, respectively. Significant difference in Gankyrin protein was found between ectopic and eutopic endometrium of OEM, ectopic and normal endometrium or eutopic and normal endometrium (P<0.0125). Higher positive expression rate for GPER was also observed in eutopic endometrium from OEM during proliferative phase in comparison to secretory phase (P<0.05). There was no significant difference in Gankyrin between proliferative and secretory phase (P>0.05). These two proteins were positively correlated with the revised American Society for Reproductive Medicine (rASRM) stages of OEM. Both of them were found to be significantly higher in advanced stages (III-IV) compared with those in early stages (I-II, P<0.05). Moreover, a significant positive correlation was found between GPER and Gankyrin proteins in ectopic endometrium of OEM (rs=0.640, P<0.01). 
 CONCLUSION GPER and Gankyrin might be involved in the pathogenesis of OEM, which could possibly facilitate the formation of ectopic lesions.
Case-Control Studies ; Endometriosis ; metabolism ; Endometrium ; pathology ; Female ; Humans ; Immunohistochemistry ; Ovary ; pathology ; Proteasome Endopeptidase Complex ; metabolism ; Proto-Oncogene Proteins ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, G-Protein-Coupled ; metabolism

OBJECTIVE: To determine the effect of progesterone on the secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in ectopic endometrial stromal cells. METHODS: Ectopic endometrial stromal cells were obtained from 17 patients with endometriosis. Endometrial stromal cells were obtained from 12 patients with endometriosis and 14 cases of controls. Ectopic endometrial stromal cells of 15 cases were treated with progesterone. Culture supernatants of these stromal cells were analyzed for MMP-2 and MMP-9 by zymography. RESULTS: Endometriotic stromal cells released significantly higher levels of MMP-2 and MMP-9 than endometrial stromal cells from women with and without endometriosis. Progesterone at 10(-9) mol/L caused endometriotic stromal cells a significant reduction MMP-2 and MMP-9 levels. When progesterone concentration was increased from 10(-9) mol/L to 10(-7) mol/L, the release of MMP-9 was almost completely inhibited, wherease that of MMP-2 was not completely inhibited. CONCLUSION Progesterone may inhibit the secretion of MMP-2 and MMP-9 in ectopic endometrial stromal cells, especially MMP-9.
Adult ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Humans ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Progesterone ; pharmacology ; Stromal Cells ; metabolism

BACKGROUNDTumors with different gene expression develop and progress in different ways. To deepen our understanding of the progression in endometrial cancer, and provide a useful tool for accurate diagnosis and prognosis assessment, we identified the new molecular prognostic markers in endometrial carcinoma and analyzed the relationship of them with clinical and pathological features of endometrial carcinoma.

METHODSNinety-four cases of endometrial endometrioid adenocarcinoma with complete data from the Peking University People's Hospital from 2000 to 2008 and 40 cases of normal endometrium were enrolled. Among these, 30 endometrial endometrioid adenocarcinoma samples of different International Federation of Gynecology and Obstetrics (FIGO) stage were selected for further Agilent genome-wide microarray analysis. Significance analysis of microarrays (SAM) was used to identify genes that are significantly associated with tumor progress. Immunohistochemistry was utilized to identify the genes of interest in endometrial carcinoma and normal endometrium. The relationship between the genes and the age, clinical stage, histological grade, myometrium invaded depth, lymph node metastasis status, and the expression of ER, PR, P53, and PTEN were analyzed by χ(2) test.

RESULTSAnalysis between FIGO 1988 stage I and stage III identified a 362-gene "progress signature"; 171 down-regulated and 191 up-regulated genes. Among the alterative genes, TARP (T cell receptor gamma alternate reading frame protein) and KRT5 (keratin 5) decreased 3.57 fold and 5.8 fold in FIGO stage III patients. The expression of TARP in endometrial carcinoma increased compared to normal endometrium, while that of KRT5 decreased (P < 0.05). The expression of TARP and KRT5 decreased when stage, histological grading, myometrium invaded depth increased (P < 0.05). In the cases with lymph node metastasis, the expression of TARP decreased, while the expression of KRT5 did not differ (both P < 0.05) both. The expression of P53 had a negative relationship with the expression of KRT5 (P < 0.05), but not with the expression of TARP (P > 0.05). There was no correlation between the expression of TARP and KRT5 and the expression of ER, PR, PTEN (all P > 0.05). There was no significant difference in TARP and KRT5 expression in patients aged 50 or younger and patients older than 50 (P > 0.05).

CONCLUSIONThe expression of TARP and KRT5 was correlated with the progress of endometrial cancer and their role needs further study.

Adult ; Aged ; Endometrial Neoplasms ; genetics ; metabolism ; Endometrium ; metabolism ; pathology ; Female ; Humans ; Keratin-5 ; genetics ; metabolism ; Middle Aged ; Nuclear Proteins ; genetics ; metabolism

OBJECTIVETo research the expression of apoptosis related genes Bcl-2 and Bax protein in dysfunctional uterine bleeding.

METHODSDetecting the expression of Bcl-2 and Bax protein in 40 cases of endometrium tissue of dysfunctional uterine bleeding patients with immunohistochemistry antibiotics protein-peroxide emzyme (SP)methods.

RESULTS(1) The expression of Bcl-2 protein changes clearly and periodically in endometrium in normal cycle, the difference is obvious (P < 0.05). (2) The Bcl-2 protein develops with the hyperplasia in endometrium and the expression intensity is enhanced, the difference is obvious( P < 0.05). (3) The expression of Bax gene is masculine in endometrium in normal menstrual cycle. (4) The expression of Bax gene descends gradually with hyperplasia in uterine endometrium (P < 0.05).

CONCLUSIONApoptosis of endometrium cell is restrained from the excessive expression of Bcl-2 protein and deficient expression of Bax protein, so the uterine endometrium gets to hyperplasia or notypical hyperplasia.

Apoptosis ; physiology ; Endometrium ; metabolism ; Female ; Gene Expression ; Humans ; Hyperplasia ; metabolism ; pathology ; Metrorrhagia ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Uterine Neoplasms ; metabolism ; pathology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVE: To investigate the inhibitory effect of gonadotropin-releasing hormone II(GnRHII) and gonadotropin-releasing hormone I agonist (GnRH Ia) on the proliferation of endometrial stromal cells in vitro from endometriosis patients. METHODS: Different concentrations of GnRHII or GnRH Ia were added into the cultured endometrial stromal cells in vitro to detect the cell proliferation inhibition by MTT test. RESULTS: The inhibitory rate of GnRHII or GnRH Ia on eutopic and ectopic endometrial stromal cells in vitro was both dose- and time-dependent (P<0.05). Effect of GnRHII or GnRH Ia on the inhibitory rate of ectopic endometrial stromal cells was significantly higher than that of eutopic (P<0.05). GnRH II had a higher inhibitory rate on the endometrial stromal cells in vitro than did GnRH Ia (P<0.05). CONCLUSION GnRHII has more antiproliferative effect on endometrial stromal cells than GnRH Ia in vitro, especially on ectopic endometrial stromal cells, suggesting that GnRHII may be more effective than GnRH Ia on endometriosis.
Adult ; Cell Proliferation ; drug effects ; Cells, Cultured ; Endometriosis ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Gonadotropin-Releasing Hormone ; agonists ; analogs & derivatives ; pharmacology ; Humans ; Middle Aged ; Stromal Cells ; pathology ; Young Adult