Mortalin expression in cervical squamous-cell carcinoma and its effect on tumor metastasis

AIM: To investigate the significance of mortalin expression in clinical pathology of cervical squamous-cell carcinoma. METHODS: Immunofluorescence staining was used to detect the location of mortalin in human cervical squamous-cell carcinoma SiHa cells. The protein expression of mortalin was detected in 59 cases of normal cervical epithelial tissues and 93 cases of cervical squamous-cell carcinoma tissues by immunohistochemical staining, and its correlation with clinicopathological features of cervical squamous-cell carcinoma was also analyzed. MTT assay was used to evaluate the optimal concentration and dosing time of mortalin inhibitor MKT-077. After the protein expression of mortalin in SiHa cells was inhibited, wound-healing and migration assays were performed. The protein expression of epithelial-mesenchymal transition (EMT)-related molecules was determined by Western blot. RESULTS: Immunofluorescence staining showed that mortalin was located in the cytoplasm of SiHa cells. The positive rate and strongly positive rate of mortalin in the cervical squamous-cell carcinoma patients were 88.7% (55/62) and 61.3% (38/62), respectively, and they were significantly higher than those in normal cervical epithelial tissues (23.7% and 5.1%, P < 0.01). Additionally, mortalin expression was statistically correlated with the histological grade, clinical stage and lymph node metastasis. After inhibiting the expression of mortalin in the SiHa cells by MKT-077, the results of wound-healing and migration assays showed that the migration ability of SiHa cells was down-regulated. The protein expression of E-cadherin was up-regulated, and vimentin and Snail were significantly down-regulated. CONCLUSION: Mortalin over-expression is an effective biomarker for prediction of malignant potential and poor prognosis of cervical squamous-cell carcinoma.     

Differential expression of Golgi mannosidaseⅡ in different differentiated gastric carcinoma cell lines and tissues

AIM: To explore the role of Golgi mannosidase Ⅱ(GMⅡ) in the development of gastric carcinoma by analysis of the relationship between differential expression of GMⅡ and differentiation of gastric carcinoma cell lines and tissues. METHODS: Thirty cases of human normal gastric tissues and 38 cases of gastric adenocarcinoma tissues were selected. Three different differentiated gastric carcinoma cell lines (MKN-28, SGC-7901 and BGC-823) and a normal gastric epithelial cell line GES-1 were cultured in vitro. The mRNA levels of GMⅡ were detected by RT-PCR, and the protein expression was detected by immunohistochemistry and Western blotting. RESULTS: GMⅡ was mainly distributed in cytoplasm. The positive rates of GMⅡ in 30 cases of human normal gastric tissues, 8 cases of well-differentiated, 18 cases of moderately-differentiated and 12 cases of poorly-differentiated gastric cancer tissues were 53% (16/30), 63% (5/8), 83% (15/18) and 100% (12/12), respectively. The expression of GMⅡ was gradually increased in normal gastric epithelial cell line and in well, moderately and poorly-differentiated gastric cancer cell lines by cell-attached coverslip. Compared with normal gastric epithelial cell line, 3 gastric carcinoma cell lines showed the higher expression of GMⅡ at mRNA and protein levels (P<0.05). Furthermore, GMⅡ expression in poorly-differentiated gastric carcinoma cell line BGC823 was the highest, and the lowest expression of GMⅡ was the well-differentiated cell line MKN-28. Compared with normal gastric epithelial tissues, gastric carcinoma tissues showed the higher expression of GMⅡ at mRNA and protein levels (P<0.05), and the highest was the poorly-differentiated carcinoma tissues. The expression of GMⅡ at mRNA and protein levels in normal gastric tissues was the lowest. CONCLUSION: GMⅡ is involved in the development and progression of gastric cancer. The expression of GMⅡ is highly related to the poorly-differentiated gastric cancer.     

Diffusion effect of malignant tumor in cervix observed by 3.0T magnetic resonance imaging

AIM: To investigate the diffusion effect of malignant tumor in cervix by diffusion weighted imaging (DWI) of magnetic resonance imaging (MRI).METHODS: Routine MRI sequences and axial diffusion weighted sequences were performed in the cases of cervical cancer and endometrial carcinoma. Normal cervixes and endometria were served as controls. The ADC values of cervical cancer and normal cervix, endometrial carcinoma and normal endometrium were measured and analyzed respectively.RESULTS: (1)The ADC values in 37 cases of cervical cancer and normal cervix of 16 volunteers were (0.92±0.20)×10-3 mm2/s and (1.26±0.24)×10-3 mm2/s respectively, with statistically significant difference between cervical cancers and normal cervixes (P<0.01). (2)The ADC values in 14 cases of endometrial carcinoma and normal endometrium of 14 volunteers were (0.87±0.17)×10-3 mm2/s and (1.34±0.26)×10-3 mm2/s respectively, with statistically significant difference between endometrial carcinoma and normal endometria (P<0.01).CONCLUSION: The diffusion effects of cervical cancer and endometrial carcinoma were different from those of normal cervical tissues. The DWI of 3.0T MRI may be used to quantitatively determine the limitation of diffusion effect in the malignant tumor in cervix by measuring the ADC value.     

Relationship between helper T lymphocytes immune deviation and class Ⅱ MHC antigen expression in acute rejection of transplanted heart

AIM: To observe the relationship between the immune deviation of Th1 and Th2 cell clones and class Ⅱ major histocompatibility complex (MHC) antigen expression in different stages of acute rejection in transplanted hearts. METHODS: Heart transplantation were performed in rats.Isografts and non-transplanted animals were used as control group. Donor class II MHC antigen expression were detected with monoclonal antibodies and immunostaining technique and the amount of type Ⅰ and Ⅱ cytokines mRNA expression were detected by semiquantitative RT-PCR in cardiac allografts. RESULTS: Myocardial IL-2 mRNA and donor class Ⅱ MHC antigen expression were significantly in-creased, accompanied with development of acute rejection (P<0.01). However, IL-4 mRNA decreased significantly (P<0.01). The immune deviation between type Ⅰ and Ⅱ cytokines mRNA expression occurred in the rejecting stage at which the cardiac allograft tissue infiltrated by multiple foci of lymphocytes and class Ⅱ MHC antigen became highly expressed. CONCLUSION: There was correlationship between Th cells immune deviation and donor class Ⅱ MHC antigen expression in the process of acute rejection in cardiac allografts. Immune deviation of T cells may facilitated the expression of donor MHC class Ⅱ antigen on transplanted heart.     

Interaction of polymorphisms of ICAM-1 gene K469E and MCP-1 gene -2518A/G in invasion and metastasis of gastric carcinoma

AIM: To investigate the interaction of polymorphisms of intercellular adhesion molecule-1 (ICAM-1) gene K469E and monocyte chemoattractant protein-1 (MCP-1) gene -2518A/G in the invasion and metastasis of gastric carcinoma. METHODS: Based on TNM classification, 4 500 patients with confirmed gastric carcinoma from the First Affiliated Hospital of Xinxiang Medical University in China from December 2009 to November 2014 were divided into stageⅠ group, stage Ⅱgroup, stage Ⅲ group, stage Ⅳ group, and stage 0 group, with 900 cases in each group. No significant difference among the 5 groups in age, gender, ethnicity, birthplace and living habit was observed. The genetic polymorphisms of ICAM-1 gene K469E and MCP-1 gene -2518A/G were analyzed by the technique of polymorphism-polymerase chain reaction (PCR) in peripheral blood leukocytes of above-mentioned cases. RESULTS: Statistical tests showed signi-ficant differences in the frequencies of K469E (EE) and -2518A/G (GG) among each group (P<0.01). The risk of the invasion and metastasis of gastric carcinoma significantly increased in subjects with K469E (EE) genotype and in those with -2518A/G (GG) genotype. Combined analysis of the polymorphisms showed that distribution frequency of K469E (EE)/-2518A/G (GG) in stage Ⅰ group, stage Ⅱ group, stage Ⅲ group, stage Ⅳ group and stage 0 group was 39.22%, 53.22%, 59.22, 65.44% and 12.11%, respectively (P<0.01). The people who carried with K469E (EE)/-2518A/G (GG) had a high risk of the invasion and metastasis of gastric carcinoma, and statistical analysis suggested a positive interaction in a super-multiplicative model between K469E (EE) and -2518A/G (GG) in increasing the risk of the invasion and metastasis of gastric carcinoma. CONCLUSION: ICAM-1 gene K469E (EE) and MCP-1 gene -2518A/G (GG) are the risk factors in the invasion and metastasis of gastric carcinoma, and significant interactions between genetic polymorphisms of K469E and -2518A/G added the risk of the invasion and metastasis of gastric carcinoma.     

Relationship between genetic instability of nm23H1 gene and clinical pathological characteristic in hepatocellular carcinoma

AIM: The aim of this study was to examine the microstatellite instability (MSI) and loss of heterozygosity(LOH) of locus D17S396 on chromosome 17 and their influence on the expression of nm23H1 in hepatocellular carcinoma (HCC),which may provide experimental evidence for the mechanism of nm23H1 gene and tumor metastasis.METHODS: Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues,PCR-SSCP,ordinary silver stain were used to study MSI and LOH of locus D17S396.Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of nm23H1.RESULTS: ① The frequency of heredity instability of HCCs was 35.42%.The frequency of LOH in the cases with lymph node or distant organs metastasis or not and with intrahepatic metastasis or embolus of portal vein or not was significantly different (P<0.01),it was higher in stage TNM Ⅲ than that in stageⅠ and Ⅱ.Moreover,it was higher in high tendency to invasion or metastasis cases than that in the low tendency cases (P<0.01).② The expression of nm23H1 was 56.25%.It was significantly different in Edmondson grade,TNM stage and in lymph node or distant organ metastasis cases (P<0.01).The cases with high tendency of invasion or metastasis exhibited lower nm23H1 expression compared with low tendency cases (P<0.01).③ The positive rate of nm23H1 protein in LOH positive group was lower than that in LOH negative group (P<0.05).CONCLUSION: The results indicate that both MSI and LOH of nm23H1 gene control the development of HCC independently in different pathways.LOH inhibits the expression of nm23H1,which endows it with high aggressive and poor prognosis.Increase in the amount of nm23H1 protein expression effectively restrains the tendency to invasion or metastasis of HCCs and improves prognosis of patients.     

Molecular mechanism of miR-1246 enhancing radiosensitivity of cervical cancer cells

AIM: To investigate the molecular mechanism of microRNA-1246(miR-1246) enhancing radiosensitivity of cervical cancer cells. METHODS: Cervical cancer lines HeLa, CaSki, C33A and SiHa were transfected with miR-1246 mimic and negative control mimic (NC-mimic) using Lipofectamine 2000 kit, and the expression level of miR-1246 in cervical cancer tissue, normal tissue, cervical cancer cell lines and endometrial epithelium cell line ESC was detected by real-time PCR. The transfected cells were exposed to X-ray radiation. The cell viability and migration rate were measured respectively by MTT assay and Transwell method. The protein levels of γH2AX, ATM, p-ATM and p-p53 were monitored by immunofluorescence and Western blot. RESUITS: Higher miR-1246 level was found in normal tissue and ESC cells, while lower miR-1246 level was found in HeLa, SiHa, C33A and Caski cells and cervical cancer tissues. The expression level of miR-1246 in the cells transfected with miR-1246 mimic was significantly higher than that in the cells transfected with NC-mimic (P<0.05). The cell viability and migration rate of the cervical cancer cells with miR-1246 over-expression were notably lower than those of the cells transfected with NC-mimic (P<0.05) under the same conditions. The results of immunofluorescence indicated that the protein expression level of γH2AX significantly increased in the cervical cancer cells with miR-1246 over-expression exposed to radiation compared with the negative control (P<0.05). The protein expression level of γH2AX was significantly increased in the cervical cancer cells with miR-1246 over-expression, while the protein levels of p-ATM and p-p53 were significantly decreased as compared with the negative control group (P<0.05). CONCLUSION: miR-1246 is highly expressed in normal tissue and normal endometrial epithelial cells, while is low expressed in the cervical cancer tissues or cells. miR-1246 over-expression inhibits growth and migration, and significantly enhances radiosensitivity of cervical cancer cells. The molecular mechanism is possibly related to inhibiting ATM pathway and DNA damage repair.     

Expression of adhesion molecules in hepatocellurlar carcinoma and its clinical significance

AIM: To investigate the expression of adhesion molecules in hepatocellular carcinoma (HCC), and analyze its clinical significance. METHODS: The expressions of adhesion molecules of tumor tissues of 64 cases and adjacent tissues of 12 cases of HCC were detected with RT-PCR. RESULTS: ①The expression rates of E-cadherin, ICAM-1, CD44, CD44V, α₅, β₁ were 90.62%, 93.75%, 50.00%, 96.88%, 100%, 100%, respectively, and there was a significant difference between CD44 and other adhesion molecules. ②The expression level of E-cadherin, ICAM-1, CD44, CD_44V, α₅,β₁ in liver cancer tissues were 1.24±0.54, 0.96±0.37, 0.62±0.73, 0.86±0.33, 0.97±0.49, 1.41±0.24, respectively, and there was a significant difference between CD44 and E-cadherin, β₁. ③The expression level of E-cadherin and CD44 mRNA declined as HCC stage become higher, and there was a statistical difference in the expression level of CD44 mRNA between Ⅰ-Ⅱ stage and Ⅳ stage. The expression level of ICAM-1, α₅, β₁ had a trend to rise as HCC stage become higher, and there was a statistical difference in the expression level of ICAM-1 between Ⅰ-Ⅱ stage and Ⅳ stage. ④The expression level of ICAM-1,CD_44V, α₅, β₁ had positive correlation with tumor volume, tumor nodules, tumor metastasis, and had negative correlation with tumor encapsulation. E-cadherin and CD44 had negative correlation with tumor volume, tumor nodules, tumor metastasis, and had positive correlation with tumor encapsulation. All showed no significant correlation with the level of AFP , the degree of cirrhosis and the function of liver. CONCLUSION: There was a significant difference in the expression level of adhesion molecule mRNA in HCC, and their expression had Spearman correlation with each other. The expression level of adhesion molecule mRNA is associated with tumor volume, tumor nodules and tumor metastasis.     

Expression of midkine and its clinical significance in transitional cell carcinoma of human urinary bladder

AIM: To investigate the expression of midkine in bladder transitional cell carcinoma and to analyze its relationship with the features of clinical pathology and prognosis.METHODS: The expressions of midkine protein in 50 cases of bladder transitional cell carcinoma samples were detected by SP immunohistochemical method using polyclonal antibodies against human midkine.Survival time of 40 cases was recorded.RESULTS: The protein expression of midkine was found in cytoplasm of tumor cells.The overall positive rate of midkine in 50 cases of bladder carcinoma was 90% (45/50).The positive degree of midkine showed a trend of increasing in grade and stage.There was statistically significant difference among them (P<0.05),but not with sex,age,treatment or tumor number and size (P>0.05).Patients with high expression of MK predicted a poor clinical outcome.CONCLUSION: Midkine is overexpressed in bladder transitional cell carcinoma than that in normal bladder.MK expression in bladder cancer is higher in less differentiated and deeper invaded cases,but it has no correlation with age,sex,treatment,tumor number and size.Patients with higher MK expression have shorter survival time than those with lower MK expression.     

Prognostic significance of FOXA1 and BRCA1 expression in triple negative breast cancer

AIM: To investigate the expression of forkhead box protein A1(FOXA1) BRCA1 protein,P53 and vascular endothelial growth factor (VEGF) in triple negative breast cancer (TNBC) and non-TNBC, and the relevance with the clinicopathological parameters for evaluating the prognosis. METHODS: The tumor samples were collected from 113 cases of breast cancer patients in the First Affiliated Hospital of Jinan University,and divided into TNBC group, luminal subtype group and HER-2 overexpression subtype group by the immunohistochemical results of estrogen receptor, progesterone receptor and HER-2. EnVision two-step method was used to detect the expression of FOXA1, BRCA1, P53 and VEGF in the tumor samples. RESULTS: Total FOXA1 positive expression rate was 63.7% (72/113), with 45.2% (19/42) in TNBC, 88.0% (44/50) in luminal subtype and 42.9% (9/21) in HER-2 overexpression subtype.The statistically sigfnificant difference among the 3 groups was observed (P<0.01). Total BRCA-1 positive expression rate was 47.8% (54/113), with 66.7% (28/42) in TNBC, 44.0% (22/50) in luminal subtype and 19.0% (4/21) in HER-2 overexpression subtype.The statisticallysignificant difference among the 3 groups was also observed (P<0.01). In the cases of clinical stages Ⅰ~Ⅱand histological grades 1~2, FOXA1 positive rate was higher than the FOXA1 negative rate (P<0.01). Negative correlations between FOXA1 positive rate and expression of P53/VEGF, and between FOXA1 positive rate and the recurrence rate were found (P<0.05). In the cases of clinical stages Ⅱ~Ⅲ and histological grades 2~3, the BRCA1 positive rate was higher than the BRCA1 negative rate (P<0.05). Positive correlations between BRCA-1 positive rate and the expression of P53/VEGF, and between BRCA1 positive rate and the recurrence rate were also observed (P<0.05). CONCLUSION: Expression of FOXA1 and BRCA1 in breast cancer is different. BRCA1 may be an adverse prognostic indicator for triple negative breast cancer.     

Serum sCD44s and sCD44v6 levels in breast cancer patients

AIM: To explore the clinical significance of detecting sCD44s and sCD44v6 in breast carcinoma. METHODS: Levels of serum soluble CD44 standard (sCD44s) and CD44 variant 6(sCD44v6) were detected by ELISA in 38 cases of breast cancer, 15 cases of benign breast diseases and 40 normal controls. RESULTS: The serum levels of sCD44s and sCD44v6 were significantly higher in patients with breast cancer than those with benign disease or normal controls. The serum concentrations of sCD44s and sCD44v6 in patients with stage Ⅲ, Ⅳ were significantly higher than those in patients with stageⅠ, Ⅱ(P＜0.01) .The level of sCD44v6 decreased markedly after one week operation and even more decreased after two weeks operation. The level of sCD44s was decreased significantly after two weeks operation. CONCLUSION: Serum levels of sCD44s and sCD44v6 may be a useful marker in the diagnosis and treatment of breast cancer. The changes in the levels of serum sCD44s and sCD44v6 may be the result of tumor burden, hence implicated in the prognosis of cancer patients.     

Expression of HDAC6 protein in cervical carcinoma tissues and its clinical significance

AIM:To investigate the protein expression of histone deacetylase 6(HDAC6) in cervical carcinoma tissues and its clinical value. METHODS:The method of immunohistochemistry was used to detect the protein expression of HDAC6 in 63 cases of cervical carcinoma tissues, 38 cases of cervical intraepithelial neoplasia(CIN) tissues and 63 cases of normal cervical epithelial tissues. The relationships between the protein expression of HDAC6 and clinical pathological features were analyzed. The protein expression of HDAC6 in randomly selected 4 cases of cervical carcinoma tissues and paired normal cervical epithelial tissues was detected by Western blotting. RESULTS:Positive rates of HDAC6 protein expression in cervical carcinoma tissues were significantly higher than that in CIN tissues or normal cervical epithelial tissues, and there were obvious differences among the 3 groups(P<0.05). The protein expression of HDAC6 was not related to age and histological differentiation(P>0.05), but closely associated with clinical stages, invasive depth and lymph node metastasis(P<0.01 or P<0.05). Furthermore, the result of Western blotting demonstrated that the protein level of HDAC6 in cervical carcinoma tissues was markedly higher than that in normal cervical epithelial tissues. CONCLUSION:HDAC6 may be an important molecular marker for evaluating malignant degree and prognosis of cervical carcinoma.     

Relationship between genetic instability of nm23H1 gene and clinical pathological behaviors in gastric cancer and colonic cancer

AIM: To study the relationship between genetic instability of nm23H1 gene and clinical pathological behaviors in Chinese with gastric cancer and colonic cancer, and provide experimental basis for the mechanism of nm23H1 gene and tumor metastasis. METHODS: This study was conducted on 40 gastric carcinomas and 30 colonic carcinomas. Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues, PCR-SSCP, ordinary silver stain were used to study microsatellite instability (MSI) and loss of heterozygosity (LOH) of locus D17S396. Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of nm23H1 protein. RESULTS: In both gastric cancer and colonic cancer, the frequency of MSI was higher in TNM stageⅠandⅡthan that in stage Ⅲ and Ⅳ, while LOH was just opposite. Moreover, the frequency of LOH in lymph node metastasis cases was significantly higher than that without lymph node metastasis cases. The positive frequency of nm23H1 protein with lymph node metastasis was lower than that without lymph node metastasis cases. TNM stage III and IV also exhibited lower nm23H1 protein positive frequency compared with stage I and II. CONCLUSION: MSI and LOH can control the carcinogenesis and metastasis of gastric cancer and colonic cancer through different approaches. MSI may be an early period molecule marker of gastric cancer and colonic cancer. In contrast, LOH appears mostly in the late period of gastric cancer and colon cancer, indicating a high aggressive and poor prognosis.     

Protein and mRNA expression of KAI1 metastasis suppressor gene and its clinical significance in cervical carcinoma

AIM: To study the mRNA and protein expression of Kang ai1 (KAI1) tumor suppressor gene and to determine the relationship between KAI1 and invasiveness and metastasis of cervical cancer. METHODS: The expression of KAI1 metastasis suppressor was detected by immunohistochemistry in paraffin slides and by real-time quantitative polymerase chain reaction (RT-PCR) in fresh tissue. The samples included 20 cases of normal cervical tissues, 20 cases of cervical intraepithelial neoplasia (CIN) and 40 cases of cervical carcinoma. The results of the gene expression combined with the pathological and clinical data were also analyzed. RESULTS: The expression of KAI1 protein and mRNA was related to the tissue differentiation of cervix. The positive rates of KAI1 expression were the highest in the normal cervical tissue, the middle in CIN and the lowest in cervical carcinoma with significant difference among three groups (P<0.01). The expression of KAI1 protein was not related with the grade of CIN (P>0.05). However, both mRNA and protein expression of KAI1 were related to the differentiation and the clinical stages of cervical cancer (P<0.01) and also related to the metastasis of the cancer. The positive rates between the non-lymphatic metastasis and lymphatic metastasis (P<0.05) were significant different. Cox regression and logistic regression showed that the tissue differentiation, clinical stages, lymphatic metastasis and expression of KAI1 were all related factors with recurrence and prognosis of cervical cancer. CONCLUSION: The down-regulation of KAI1 tumor suppressor gene at both mRNA and protein levels is related to the differentiation, clinical stages and metastasis of cervical cancer, indicating that the expression of KAI1 is a prognostic factor for cervical cancer.     

Clinical significance of STMN1 expression in cervical cancer and effect of inhibition of its expression on viability and apoptosis of cervical cancer SiHa cells

AIM: To investigate the clinical significance of stathmin 1 (STMN1) expression in cervical cancer and the influence of its expression on the viability and apoptosis of cervical cancer cells. METHODS: Western blot was used to detect the protein expression of STMN1 in cervical cancer tissues, and the relationship between the expression and clinical characteristics of cervical cancer was analyzed. STMN1-siRNA was transfected into cervical squamous-cell carcinoma SiHa cells. The protein levels of STMN1, STAT3, p-STAT3 and survivin were determined by Western blot after transfection for 48 h. The cell viability was measured by MTT assay. The apoptosis was analyzed by flow cytometry. DCFH-DA probe was used to detect the level of reactive oxygen species (ROS). RESULTS: The protein expression of STMN1 in cervical cancer tissues was significantly higher than that in paracancerous tissues (P<0.01). The STMN1 protein expression level was not correlated with age and histological types of cervical cancer patients, but was related to clinical stage, histological differentiation and lymph node metastasis (P<0.01). Transfection with STMN1-siRNA significantly reduced the expression of STMN1 in SiHa cells. Compared with control group, the cell viability in STMN1-siRNA group was significantly decreased, the apoptotic rate and ROS content were increased, and the protein levels of p-STAT3 and survivin were down-regulated (P<0.01). However, no significant difference of the STAT3 protein level was observed between STMN1-siRNA group and control group. CONCLUSION: STMN1 is highly expressed in cervical cancer, and its expression is related to clinical stage, histological differentiation and lymph node metastasis. Inhibition of STMN1 expression reduces the viability and promotes apoptosis of cancer cells by down-regulating STAT3 signaling pathway.     

Expression of EphA2 and ephrin-A1 in endometrial endometrioid adenocarcinoma and their relationship with angiogenesis

AIM: To investigate the expression of erythropoietin-producing hepatocellular receptor A2 (EphA2) and its ligand ephrin-A1 in endometrial endometrioid adenocarcinoma (EEA), and to analyze their relationship with angiogenesis of the tumor. METHODS: The CD34-stained microvessel density (MVD) and the expression of ephA2 and ephrin-A1 were detected by immunohistochemical assay in 56 cases of EEA, 20 cases of endometrial hyperplasia, 30 cases of normal proliferative endometrium and 30 cases of normal secretory endometrium. The correlations among the expression of EphA2 and ephrin-A1, MVD and clinicopathological features were analyzed. RESULTS: MVD and the expression of EphA2 and ephrin-A1 in EEA were significantly higher than those in the tissues from endometrial hyperplasia and normal endometrium (P<0.05). They were related to FIGO stage, histological differentiation, depth of myometrial invasion, lymphovascular invasion and progesterone receptor expression (P<0.05). A significant positive correlation between MVD and the expression of EphA2 and ephrin-A1 was observed by Spearman rank correlation test (r=0.476, P<0.05; r=0.501, P<0.05). CONCLUSION: Overexpression of EphA2 and its ligand ephrin-A1 in EEA may be involved in the angiogenesis and progesterone resistance.