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Recent studies reported the presence of oncogenic mutations in normal endometrial glands, but the biological significance remains unclear. The present study investigated the status of KRAS/PIK3CA driver mutations in normal endometrial glands as well as spheroids derived from single glands. The normal endometria of surgically removed uteri (n = 3) were divided into nine regions, and 40 endometrial single glands were isolated from each region. The DNAs of 10 glands in each region were extracted and subjected to Sanger sequencing for KRAS or PIK3CA driver mutations, while the remaining 30 glands were conferred to a long‐term spheroid culture, followed by Sanger sequencing. Immunohistochemical analyses of stem cell (Axin2, ALDH1A1, SOX9) markers were undertaken for spheroids. Sanger sequencing successfully detected oncogenic mutations of KRAS or PIK3CA in a single gland. Twenty‐five of the 270 glands (9.3%) had mutations in either KRAS or PIK3CA, and the mutation frequency in each endometrial region varied from 0% to 50%. The droplet digital PCR showed high mutation allele frequency (MAF) of PIK3CA mutation, suggestive of clonal expansion of mutated cells within a gland. Over 60% of the collected spheroids had PIK3CA mutations, but no KRAS mutations were detected. Immunohistochemically, spheroids were mainly composed of cells with stem cell marker expressions. High MAF of PIK3CA mutation in a single gland as well as frequent PIK3CA mutation in stem cell‐rich spheroids that originated from a single gland suggest the role of PIK3CA mutation in stem cell propagation. This information could improve our understanding of endometrial physiology as well as stem cell‐oriented endometrial regeneration and carcinogenesis. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSC) are a potential cause for recurrence, metastasis, and resistance of tumors to different therapeutic modalities like hormonal radiotherapy and chemotherapy. We investigated two CSC markers (NANOG and CD 133) in normal, hyperplastic endometrium and endometrial carcinoma. A total of 93 formalin-fixed paraffin-embedded tissue blocks were used for immunohistochemical expression of NANOG and CD133 markers. NANOG expression was detected in 88.37% of endometrial carcinoma cases compared to 15% of the normal proliferative endometrium and 60% of hyperplasia cases. In endometrial carcinoma, high NANOG expression was significantly correlated with high grade, deep myometrial invasion, lymph node metastasis, and high stage with p-values (0.009, 0.005, 0.014, and 0.003, respectively). CD133 was positive in 76.74% of endometrial carcinoma cases, and it showed a significant correlation with deep myometrial invasion, positive lymph node, positive lymphovascular invasion, and high stage (p-values 0.003, 0.001, 0.003, and 0.013, respectively). Normal endometrium showed less expression of CD133 (only 5%) than hyperplasia and endometrial carcinoma with a statistically highly significant difference (p less than 0.0001). Hyperplastic cases with atypia expressed higher CD133 than those without atypia (6 out of 12 versus 3 out of 18). However, this difference was not statistically significant (p-value 0.111). The cancer stem cell markers NANOG and CD 133 are expressed in a high percentage in endometrial carcinoma compared to normal and hyperplasia and their expression is positively correlated with the aggressive behavior of the tumor. High expression of these two markers in apparently normal tissue around the tumor and in hyperplastic conditions with atypia suggests the possibility to use NANOG and CD133 expression as a diagnostic marker distinguishing dysplasia from reactive atypia. Therefore, inhibition of these markers can be a promising method to stop the progression of early cancers. [ABSTRACT FROM AUTHOR]

The human endometrium is an essential component in human reproduction that has the unique characteristic of undergoing cyclic regeneration during each menstrual cycle. Vigorous regeneration after shedding may be sustained by stem/progenitor cells, for which molecular markers have not been fully identified. Although clonality analysis using X chromosome inactivation patterns has shown that normal human endometrial glands are composed of a monoclonal cell population, whether clonal expansion is derived from stem/progenitor cells remains unclear. Remarkable advances in next‐generation sequencing technology over the past decade have enabled somatic mutations to be detected in not only cancers, but also normal solid tissues. Unexpectedly frequent cancer‐associated mutations have been detected in a variety of normal tissues, and recent studies have clarified the mutational landscape of normal human endometrium. In epithelial glandular cells, representative cancer‐associated mutations are frequently observed in an age‐dependent manner, presumably leading to growth advantage. However, the extremely high mutation loads attributed to DNA mismatch repair deficiency and POLE mutations, as well as structural and copy number alterations, are specific to endometrial cancer, not to normal epithelial cells. The malignant conversion of normal epithelial cells requires these additional genetic hits, which are presumably accumulated during aging, and may therefore be a rare life event. These discoveries could be expected to shed light on the physiology and pathogenesis of the human endometrium and urge caution against the application of genetic screening for the early detection of endometrial cancer. [ABSTRACT FROM AUTHOR]

Endometrial cancer is the sixth most common neoplasm in women worldwide, with a rising incidence largely attributed to the ongoing obesity epidemic. TNF-Related Apoptosis-Inducing Ligand (TRAIL) and TRAIL receptors have been tested for their predictive, diagnostic, and prognostic values in various cancers, as well as for possible use in combination therapies. The roles of TRAIL and its receptors in endometrial tissue biology has not yet been cleared, and the potential of these molecules as biomarkers in endometrial cancer is yet to be defined. We investigated the expression profiles of TRAIL and its transmembrane receptors during endometrial carcinogenesis to evaluate their potential as prognostic markers. Paraffin-embedded normal endometrium (n=18), endometrial hyperplasia (n=27), and endometrioid endometrial adenocarcinoma tissues (n=100) were analysed for TRAIL and receptor expression profiles via immunohistochemical staining. Apoptotic indexes in the corresponding tissues were defined by TUNEL assay. Endometrial carcinoma displayed decreased TRAIL and DR4 expressions compared to the normal endometrium, while increased DR5 and decoy receptor (DcR1 and DcR2) expressions were evident. The complex atypical hyperplasia displayed the most similar expression profiles to the endometrial carcinoma, in accordance with the greatest risk of progression to endometrial carcinoma attributed to this tissue type. TRAIL/TRAIL receptor expression levels did not correlate with the prognostic factors of tumor stage or grade, or depth of myometrial invasion. Overall, distinct profiles of TRAIL and its receptor expressions were evident in progression from normal endometrium to hyperplasia and cancer, which may indicate significance of TRAIL signaling in the course of endometrial carcinoma development. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the role of NOX4 in the biology of the normal endometrium and endometrial cancer. NOX4 plays a key role in other adenocarcinomas and has been implicated in the pathogenesis of diabetes and obesity, which are important risk factors for endometrial cancer. NOX4 expression was assessed in 239 endometrial cancer and 25 normal endometrium samples by quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry. DNA methylation of the NOX4 promoter was determined by means of MethyLight PCR. Data were correlated with clinicopathological parameters and analyzed in the context of diabetes and body mass index. In the normal endometrium, NOX4 microRNA expression was significantly higher in the secretory transformed compared with proliferative endometrium (p = 0.008). In endometrial cancer specimens, NOX4 expression did not differ between diabetic and non-diabetic patients, but was the highest in patients with a body mass index ł 26 (p = 0.037). The lowest NOX4 expression was found in carcinosarcomas (p = 0.007). High NOX4 expression predicted poorer clinical outcome with regard to overall survival, especially in non-diabetic patients and those with a body mass index.20. Independent prognostic significance of NOX4 transcripts was retained in type I endometrial cancer and was the most meaningful in patients with a body mass index.20. No prognostic impact was shown for NOX4 promoter methylation in endometrial cancer. For the first time, we demonstrate that NOX4 plays a considerable role in the cycle-dependent changes in the normal endometrium and in the biology of endometrial cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the membrane expression of DR4, DR5, DcR1 and DcR2 in the normal endometrium (NE), atypical endometrial hyperplasia (AEH) and endometrioid adenocarcinoma (EAC). Methods: The study comprised 197 patients: 20 NE, 18 AEH and 159 EAC. Tissue microarrays were constructed. Membrane expression of DR4, DR5, DcR1 and DcR2 was examined and presented as total score (TS). Results: In EAC, the membrane expression of DR4, DR5 and DcR2 was less common compared to NE ( p < 0.001; p < 0.001; p = 0.018) and AEH ( p < 0.001; p < 0.001; p = 0.004). In EAC the membrane expression of DcR1 did not differ when compared to NE ( p = 0.055) and AEH ( p = 0.173). A strong correlation was found between the type of endometrial tissue (NE/AEH/EAC) and the TS of DR4 ( p < 0.001), DR5 ( p < 0.001), DcR1 ( p = 0.033) and DcR2 ( p < 0.001). In EAC, the TS of DR4, DR5, DcR1 and DcR2 was not related to grading and staging. In EAC, the membrane expression of DR5, but not DR4, DcR1 and DcR2, was related to better disease-free survival (DFS). The overall survival (OS) was not related to membrane TRAIL receptors expression. Conclusions: The membrane expression of the receptors for TRAIL DR4, DR5, DcR1 and DcR2 is greater in NE than EAC. The level of membrane staining of the receptors in EAC is not dependent on grading and staging. In EAC patients, membrane expression of DR4, DR5, DcR1 and DcR2 are not independent predictors of survival. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to examine the utility of SurePath-liquid-based cytology (LBC) compared to conventional cytological preparations (CCP) in the identification of endometrial carcinoma. Methods: During a 13-month period, direct endometrial samples were collected from 120 patients using the Uterobrush. The material comprised 30 cases each of endometrial carcinoma, proliferative endometrium, secretory endometrium and atrophic endometrium. The following points were investigated:(i) the frequency of cell clumps in endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei. Results: (i) Comparison of the frequency of cell clumps with irregular protrusion pattern and papillo-tubular pattern showed no statistically significant difference in either type of cell clump between CCP and LBC. (ii) Comparison of the nuclear area of cells showed a sequential decrease from endometrial carcinoma to secretory endometrium, to proliferative endometrium and to atrophic endometrium, which was significant in CCP and LBC. (iii) Nuclear area was significantly lower with LBC compared with CCP in endometrial carcinoma, secretory endometrium and proliferative endometrium but not atrophic endometrium. (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease from endometrial carcinoma to proliferative endometrium, to secretory endometrium and to atrophic endometrium, which was significant in both CCP and LBC. (v) Comparison of the degree of overlapping nuclei between CCP and LBC showed no significant difference for normal types of endometrium, but LBC had significantly higher values ( P < 0.0001) in endometrial carcinoma than in CCP. Conclusions: The results of this study revealed that applying diagnostic criteria used in CCP to LBC was easy to achieve, because LBC had excellent cytoarchitectural preservation and cells were well presented. Although we have not examined all cytological features of malignancy and have not considered atypical hyperplasia, we believe that this method may be a useful tool in the diagnosis of endometrial cytology. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the current study was to examine the use of thin-layer cytologic (TLC) preparation compared to conventional cytologic preparation (CCP) in the normal endometrium (proliferative, secretory, atrophic) and endometrial glandular and stromal breakdown (EGBD). During a 6-month period, we compiled 158 cases by collecting a direct endometrial sample using the Uterobrush. The material comprised 40 cases of proliferative endometrium, 42 cases of secretory endometrium, 46 cases of atrophic endometrium, and 30 cases of EGBD. The following points were investigated: (1) number of endometrial epithelial cell clumps; (2) presence of TLC > CCP cases on number of epithelial cell clumps; (3) number of condensed cluster of stromal cells; (4) presence of TLC > CCP cases on number of condensed cluster of stromal cells; (5) presence of metaplastic clumps with irregular protrusion-containing condensed stromal cluster; (6) presence of a clear background; (7) presence of blood vessel in TLC; (8) presence of blood vessel of length more than diameter of a field in object ×20 glasses in TLC. (1) In all phases, the number of epithelial cell clumps per a unit area of a preparation of TLC is greater than in CCP. (2) Cells (condensed cluster of stromal cells and metaplastic clumps with irregular protrusion-containing condensed stromal cluster) of useful and adequate numbers for a diagnosis of EGBD were observed in TLC. (3) In all phases, TLC was significantly higher than CCP on the appearance of a clear background. (4) The proliferative endometrium and secretory endometrium were highly significant in comparison with atrophic endometrium and EGBD, respectively, in terms of the occurrence of a blood vessel of length more than diameter of a field in object ×20 glasses. Although the preparation area of TLC is smaller than that of CCP, the preparation has a clean background so that an accurate report on the patient''s condition is possible. Therefore, TLC preparation is a useful tool for the accurate and reliable diagnosis of normal endometrial phase and EGBD, because the preparation area is confined and identification of the target cell clumps is easy. [Copyright &y& Elsevier]

Transforming growth factor-β (TGF-β) belongs to a superfamily of structurally related polypeptides involved in various biological processes, including cell growth, proliferation and differentiation, angiogenesis, apoptosis, and extracellular matrix remodeling. We tried to define the different expression patterns of the TGF-β receptors by investigating the female reproductive organs during the menstrual cycle and endometrial tumorigenesis, because their role in these processes is still unclear. In this study, we examined the expression of the TGF-β type I and type II receptors in normal (n=13) and carcinomatous (n=42) endometrial tissue specimens using reverse transcriptase polymerase chain reaction and immunological (Western blot and enzyme linked immunosorbent assay) methods. Two uncommon female genital tract tumors, rhabdomyosarcoma of the uterine cervix and uterine carcinosarcoma, were also included. There were no significant differences between normal and cancerous endometrial tissues regarding the TGF-β receptors mRNA levels. However, we observed a markedly low TGF-β type I receptor protein level (P<0.028; Mann–Whitney-U test), while the malignant endometrium showed a significantly higher TGF-β type II receptor protein level (P<0.007; Mann–Whitney-U test) than the normal endometrium. Moreover, significantly elevated TGF-β receptor type II protein level was noted when depth of myometrial invasion of endometrial carcinomas was considered (P<0.05; Mann–Whitney-U test). In contrast to uterine carcinosarcoma, in which no detectable mRNA for TGF-β type II receptor was found, we noted expression of both TGF-β receptors in rhabdomyosarcoma of the uterine cervix. However, neither rhabdomyosarcoma of the uterine cervix nor uterine carcinosarcoma displayed TGFβRI and TGFβRII protein expression. This observation corroborates the complexity of the deregulation of TGF-β receptor expression in human endometrial cancer. [Copyright &y& Elsevier]

Patterns of episialin/MUC1 expression in endometrial carcinomas and prognostic relevance Aims: To investigate episialin/MUC1 expression in the normal, hyperplastic and neoplastic endometrium, and relate patterns of tumour MUC1 reactivity with histopathological characteristics, oestrogen and progesterone receptor (ER and PR) status, bcl-2 and p53 oncoproteins and with clinical behaviour. Methods and results: We studied 42 normally cycling endometria, 45 endometrial hyperplasias of various forms, and 111 endometrial carcinomas of endometrioid and non-endometrioid cell types with specific monoclonal antibodies employing standard immunohistochemical techniques. The follow-up period ranged from 34 to 182 months with a median of 86 months. Epithelial mucin episialin/MUC1 was consistently expressed in the normal endometrium, following a cyclical pattern: ‘apical membrane staining’ in early and mid-proliferative endometrium; ‘purely cytoplasmic staining’ in late proliferative endometrium; and ‘cytoplasmic staining with intraluminal secretions’ in secretory endometrium. Immunostaining patterns in simple and complex hyperplasia were similar to late proliferative endometrium, while atypical hyperplasias and endometrial carcinomas either simulated patterns of proliferative endometrium or lacked MUC1 reactivity. Membranous MUC1 positivity was statistically more frequent in endometrioid carcinomas compared with carcinomas of non-endometrioid type (P = 0.006). Cytoplasmic MUC1 positivity was significantly associated with poor prognosis, while MUC1-negative carcinomas were associated with PR expression and an improved survival (P=0.04). There was no association of MUC1 patterns with bcl-2 and p53 immunoreactivity or with other histopathological variables. Conclusions: Episialin/MUC1 is an integral component of the normal premenopausal endometrium and is probably hormonally regulated. It is frequently expressed in endometrial... [ABSTRACT FROM AUTHOR]

Background. Pyrimidine nucleoside phosphorylase (PyNPase) is identical to the protein, platelet-derived endothelial cell growth factor (PD-ECGF), which has angiogenic activity. The physiological roles of PyNPase activity in the uterus and ovary are not known. In this study, we measured PyNPase activity in normal tissues of the uterus, ovary, and lymph nodes, and in benign and malignant lesions of these organs, and we considered the clinical implications of PyNPase activity in the uterus and ovary. Methods. Tissue samples were obtained from 163 patients (whose diseases are listed below) during surgery. PyNPase activity was measured spectrophotometrically, by monitoring the formation of 5-fluorouridine. Results. Mean PyNPase activity in tissues from the lesions of patients with cervical cancer ( n = 20), uterine endometrial cancer ( n = 26), leiomyoma ( n = 23), ovarian cancer ( n = 46), ovarian endometriosis ( n = 21), and benign epithelial ovarian tumor ( n = 27) was significantly greater than that in the corresponding normal tissues. The PyNPase activity in the normal endometrium was significantly higher in the secretory phase than in the proliferative phase. The activity in normal or metastatic lymph nodes was significantly greater than that in normal tissues of the uterus and ovary. Mean PyNPase activity in cancerous cervical tissues was significantly greater than that in cancerous endometrial tissues or cancerous ovarian tissues. There were no significant differences in PyNPase activity in cervical cancer, endometrial cancer, and ovarian cancer tissues according to tumor stage. The enzyme activity appeared to be greater in histopathological G3 grade endometrial cancer than in G1 and G2 endometrial cancer. The enzyme activity in mucinous adenocarcinoma of the ovary was significantly lower than that in serous, endometrioid, and clear cell adenocarcinomas. All patients with cervical squamous cell carcinomas with PyNPase activity greater than 500 nmol/min per mg protein exhibited lymph node metastasis. Conclusion. Increased PyNPase activity consistently reflected neoplastic growth, and varying levels of activity were seen in different histologic cell types. This enzyme activity may be involved in cervical squamous cell carcinomas, in normal and metastatic lymph nodes, and in the normal, secretory phase in the endometrium. [ABSTRACT FROM AUTHOR]

A silver colloid technique to identify nucleolar organizer region associated protein (AGNORs) has been applied to paraffin sections in a total of 43 endometrial hyperplasias (24 adenomatous and 19 adenocystic) 26 endometrial carcinomas and 22 normal endometria (11 of proliferative and 11 of secretory phase). A morphometric analysis of highly magnified photographic images of AGNORs in light microscopic preparations was performed. Malignant tumor cells showed significantly higher AGNOR numbers, maximum diameter and mean area compared with normal and hyperplastic endometrium, with the exception of adenocystic hyperplasia whose D and mean area were significantly larger. Regarding the distribution pattern of AGNOR dots in the cases studied, it was found that normal and hyperplastic endometrium had a mainly clustered distribution while endometrial adenocarcinomas revealed a scattered one. The significant differences observed in the number of AGNORs, their size and mean area between benign and malignant endometrial epithelia suggest that the AG-NOR staining technique is of diagnostic importance in distinguishing between these two groups. [ABSTRACT FROM AUTHOR]

Tissue culture offers a model system with which to study the endocrine-mediated growth, differentiation, and metabolic activities of the endometrium. We have established and continue to maintain monolayer cultures of normal human endometrial epithelial cells from each phase of the menstrual cycle. At present, eight proliferative, two secretory, and two menstrual phase cultures have been established. These have been passed at least three times. One proliferative phase culture has been growing for 18 mo, and passed 10 times. Colonies of epithelioid cells as well as single cells appear in the cultures within 2 to 8 h of initial culture and maintain this appearance throughout long-term growth. The cells are periodic acid Schiff positive for carbohydrates and positive for keratin, an immunochemical marker for epithelial tissues. Studies comparing the ultrastructure of the cultures with fresh endometrial tissue revealed morphologic features common to both, including prominent nucleoli, Golgi, mitochondria-rough endoplasmic reticulum complexes, and abundant glycogen. The cells are not tumorigenic in the nude mouse and do not form colonies on soft agarose, confirming the nonneoplastic identity of the cells. [ABSTRACT FROM AUTHOR]

We conducted this study to assess the effect of VDR and CRBP-1 immunohistochemical expression on the endometrium and to explore their role in endometrial cancer carcinogenesis. This study comprised two hundred paraffin-embedded endometrial tissue samples diagnosed as 42 and 63 proliferative and secretory endometrium respectively, 45 endometrial hyperplasias with atypia and 50 endometrial carcinomas (25 low-grade and 25 high-grade endometrial carcinomas). The immunohistochemical method was done to determine the expression of VDR and CRBP-1. VDR was strongly expressed in 8 (17.8%) cases with endometrial hyperplasia, 15 (60%) cases with low-grade endometrial carcinoma, and 22 (88%) cases with high-grade endometrial carcinoma. While CRPB1 overexpression was noted in cases with proliferative endometrium, secretory endometrium and endometrial hyperplasia with atypia, 37 (88.1%), 56 (88.9%) and 3 (6.7%) cases respectively and all malignant cases showed negative expression. Increased VDR expression and reduced CRBP-1 expression are associated with malignant features of the endometrium with a significant statistical difference of immunoreactivity between groups of normal endometrium, hyperplastic changes & carcinoma. Our data suggested that increased VDR expression is partly associated with endometrial cancers through a premalignant phase. Also, increased VDR and reduced CRBP-1 expression are associated with the progression of endometrial carcinoma with higher grades. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the role of NOX4 in the biology of the normal endometrium and endometrial cancer. NOX4 plays a key role in other adenocarcinomas and has been implicated in the pathogenesis of diabetes and obesity, which are important risk factors for endometrial cancer. NOX4 expression was assessed in 239 endometrial cancer and 25 normal endometrium samples by quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry. DNA methylation of the NOX4 promoter was determined by means of MethyLight PCR. Data were correlated with clinicopathological parameters and analyzed in the context of diabetes and body mass index. In the normal endometrium, NOX4 microRNA expression was significantly higher in the secretory transformed compared with proliferative endometrium ( p = 0.008). In endometrial cancer specimens, NOX4 expression did not differ between diabetic and non-diabetic patients, but was the highest in patients with a body mass index ≤ 26 ( p = 0.037). The lowest NOX4 expression was found in carcinosarcomas ( p = 0.007). High NOX4 expression predicted poorer clinical outcome with regard to overall survival, especially in non-diabetic patients and those with a body mass index > 20. Independent prognostic significance of NOX4 transcripts was retained in type I endometrial cancer and was the most meaningful in patients with a body mass index > 20. No prognostic impact was shown for NOX4 promoter methylation in endometrial cancer. For the first time, we demonstrate that NOX4 plays a considerable role in the cycle-dependent changes in the normal endometrium and in the biology of endometrial cancer.

Tumor microenvironment inflammatory cells play a major role in cancer progression. Among these, the Tumor Associated Macrophages (TAMs) infiltration depends on the kind of chemokine, cytokines and growth factors secreted by the tumor cells and by the stroma in response to the cancer invasion. TAMs have been found to promote anti-tumor response in early stages and to stimulate neovascularization and metastases in advanced disease. In the microenvironment chemo-attractants of many human cancers, MIF and VEGF correlate with an increased TAMs recruitment. In addition, MIF enhances tumor cells metastases by modulating the immune responses and by promoting the angiogenesis related to VEGF. On the contrary the inhibition of MIF can lead to cell cycle arrest and apoptosis. Some chemokines (e.g. CXCL12, CXCL11, CXCL8) and their receptors, thanks to their ability to modulate migration and proliferation, are involved in the angiogenetic process. In this study we compared the expression of MIF mRNA with VEGF mRNA expression and with mRNA expression of other chemokines related to neo-angiogenesis, such as CXCL12, CXCL11, CXCL8 and CXCR4, in human endometrial cancer tissue (EC) and normal endometrium (NE). Fresh samples of EC tissue and NE were extracted from 15 patients with FIGO stage I-III undergoing primary surgery. Some of the tissue was sent for histology and part of it was treated with RNA later and stored at -80°C. Four patients dropped out. A significant up-regulation of MIF mRNA in EC tissue versus NE samples (P=0.01) was observed in all 11 patients. The MIF mRNA over-expression was coincident with a VEGF mRNA overexpression in 54% of patients (P=NS). MIF mRNA was inversely related to CXCL12 mRNA expression (P=0.01). MIF over-expression was significantly related to low grading G1-2 (P=0.01), endometrial type I (P=0.05), no lymphovascular spaces invasion (P=0.01) and 3years DFS (P=0.01). As reported in previous studies on patients with breast cancer, our data suggest that the up-regulation of MIF in patients with endometrial cancer might be related to the inhibition of distant and lymphatic spread., (Copyright © 2013. Published by Elsevier Ltd.)