Expression In Endometrial Carcinoma Research Articles

Expression of programmed death-ligand 1 and hypoxia-inducible factor-1α proteins in endometrial carcinoma.

Programmed death-ligand 1 (PD-L1) and hypoxia-inducible factor-1α (HIF-1α) proteins mediate major alterations of tumor microenvironment including generation of immunosuppressive microenvironment and tumor hypoxia, respectively. These alterations play a crucial role in carcinogenesis and tumor progression. The present study was designed to investigate the correlation between the expression of PD-L1 and HIF-1α proteins and the clinicopathologic variables in endometrial carcinoma. Tumor tissue sections from 95 endometrial carcinomas were evaluated for PD-L1 and HIF-1α immunohistochemical protein expression. The statistical analyses were performed using Chi-square and Fisher's exact tests when appropriate. Two-sided P < 0.05 was considered statistically significant. PD-L1 and HIF-1α expression were detected in 48.4% and 68.4% of endometrial carcinomas, respectively. PD-L1 expression was significantly associated with lymph node metastasis (P = 0.027). HIF-1α expression was significantly associated with tumor grade, depth of myometrial invasion, and lymph node metastasis (P = 0.014, 0.012, and 0.046, respectively). A significant positive correlation was detected between PD-L1 and HIF-1α immunoexpression (P = 0.015). PD-L1 and HIF-1α proteins are promising potential prognostic biomarkers in endometrial carcinomas since their overexpression is associated with clinicopathologic variables of advanced disease. A potential role of HIF-1α in upregulation of PD-L1 expression is suggested based on the finding of positive correlation between PD-L1 and HIF-1α expression in endometrial carcinoma. These findings point to a potential role of biomarkers inhibitors in controlling endometrial cancer progression.

Programmed Death Ligand 1 Expression Among 700 Consecutive Endometrial Cancers: Strong Association With Mismatch Repair Protein Deficiency.

This study aims to determine the prevalence of programmed death ligand 1 (PD-L1) expression in endometrial carcinoma (EC) and determine clinical and pathological associations. Immunohistochemistry for PD-L1 was performed on sections of a triple-core tissue microarray of 700 ECs. Positive PD-L1 expression, defined as 1% of cells staining positive, was evaluated in tumor and stromal compartments. Using age-adjusted logistic regression, we estimated odds ratios and 95% confidence intervals for associations between PD-L1 expression (overall and by staining compartment) with clinical and tumor characteristics. Kaplan-Meier plots and log-rank tests were used to evaluate associations between PD-L1 expression and EC-specific survival. PD-L1 expression was observed in 100 cases (14.3%), including 27 (3.9%) with expression in tumor cells only, 35 (5.0%) with expression in both tumor cells and stroma, and 38 (5.4%) with expression in stroma only. Expression was observed in ECs of different histologic types. Tumors characterized by loss of mismatch repair proteins were significantly associated with tumoral PD-L1 expression (P < 0.0001), but not with stromal PD-L1 expression. Both tumoral and stromal PD-L1 expressions were associated with high-grade endometrioid histology, nonendometrioid histology, and lymphovascular space invasion. We observed no significant associations between PD-L1 expression and EC-specific survival. PD-L1 is expressed in a significant proportion of EC and is associated with mismatch repair deficiency, potentially representing a mechanism of tumor immune evasion and a therapeutic target in EC.

WITHDRAWN: Correlation between FOXP1 and ER/PR expression in endometrial carcinoma

WITHDRAWN: Correlation between FOXP1 and ER/PR expression in endometrial carcinoma

The Role of Hepsin in Endometrial Carcinoma

Endometrial carcinoma is the sixth most common cancer in women worldwide and the most common invasive cancer of the female genital tract in developed countries. It is hoped that through a better understanding of the alterations implicated in endometrial cancer pathogenesis and prognosis, a more complete profile of risk factors and targeted therapy can be developed. Hepsin is a member of the type II transmembrane serine protease family. The importance of hepsin in prostate cancer has been demonstrated by several studies. However, the role of hepsin in endometrial carcinoma is yet to be identified. This study aimed to evaluate the immunohistochemical expression of hepsin in endometrial carcinoma, trying to explore its diagnostic and prognostic value. This retrospective study was conducted on 27 endometrial carcinoma and 18 endometrial hyperplasia cases. Immunohistochemical expression of hepsin was evaluated in tissue specimens and results were correlated with the available clinicopathlogic parameters. Positive hepsin expression was seen in all (100%) carcinoma and 17/18 (94.44%) endometrial hyperplasia cases. The H-score of hepsin expression in endometrial carcinoma was significantly higher than that of hyperplasia cases (P=0.012). A significant negative association was found between hepsin expression in endometrial carcinoma cases regarding the grade and the size of tumors (P=0.018 and 0.008, respectively) as well as myometrial invasion (P=0.027). Hepsin could play an important role in the pathogenesis and the early carcinogenesis of endometrial carcinoma and could serve as a prognostic biomarker in this tumor.

Villin immunohistochemical expression in endometrial carcinoma

Villin immunohistochemical expression in endometrial carcinoma

Abstract 436: Glycodelin expression in endometrial carcinoma

Abstract Glycodelin is a lipocalin protein mainly expressed in well-differentiated epithelial cells in reproductive tissues, including endometrium and seminal vesicles. Previously, glycodelin has been shown to induce differentiation of endometrial carcinoma cells, which was associated with reduced xenograft tumor growth. Glycodelin is highly expressed in secretory endometrium, but not in proliferative or postmenopausal endometrium. While glycodelin is weakly, if at all, expressed in cancer tissues and, when expressed, associated with better prognosis, results regarding the expression of glycodelin in endometrial carcinoma are discordant. Therefore, we studied the expression of glycodelin in endometrial carcinoma and hyperplasia by immunohistochemical staining using highly validated antibody developed in house. Furthermore, the levels of mRNA were addressed utilizing in silico transcriptomics databases. Glycodelin transcripts were more abundant in normal uterus than in uterine carcinomas. Glycodelin staining in endometrial carcinoma sections was also much lower than that in secretory phase endometrium. Interestingly, in some endometrial hyperplasia samples glycodelin levels were much lower in hyperplastic regions of the sample as compared to those having normal histology. In conclusion, our data show that glycodelin is not highly expressed, if at all, in endometrial carcinoma tissues. This is in keeping with the reduced expression of glycodelin in postmenopausal endometrium and association of glycodelin in epithelial differentiation. Citation Format: Hannu Koistinen, Annukka Pasanen, Laura Hautala. Glycodelin expression in endometrial carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 436.

LncRNA FER1L4 suppresses cancer cell proliferation and cycle by regulating PTEN expression in endometrial carcinoma

BackgroundDysregulated long non-coding RNAs (lncRNAs) might exert key roles in pathways associated with endometrial carcinoma (EC) development. This study aims to investigate the new role of lncRNA FER1L4 in EC pathogenesis due to its correlation with phosphatase and tensin homolog (PTEN), one important indicator of EC progression. MethodsReal time PCR was performed to detect the expression of FER1L4 in thirty paired EC samples and two EC cell lines. Plasmid containing FER1L4 was transfected into HEC-50 cells with a relative lower level of FER1L4 expression, followed which PTEN expression and Akt phosphorylation were measured by western blotting. Cell proliferation was analyzed through MTT and colony-formation assays, while cell cycle and apoptosis were determined by flow cytometry. ResultsFER1L4 showed significantly downregulation in EC tissues compared to control, which was positively correlated with decreased PTEN expression. Moreover, FER1L4 could promote PTEN expression and inhibit Akt phosphorylation. Additionally, a significant decrease of cell proliferation was observed in FER1L4 overexpressing cells, along with cell cycle arrest at G0/G1 phase and increased proportion of apoptotic cells. ConclusionFER1L4 not only showed downregulation in EC tissues and cells, but also regulated PTEN expression and Akt signaling, which might contribute to its inhibition on cell proliferation. This study might provide a new potential therapeutic target for EC treatment.

Assessing sirtuin expression in endometrial carcinoma and non-neoplastic endometrium.

Sirtuins participate in hormone imbalance, metabolism and aging, which are important processes for endometrial cancer (EC) development. Sirtuins mRNA expression (SIRT1 to 7) was determined in 76 ECs (63 Type I, 12 Type II and one mixed EC), and 30 non-neoplastic endometria (NNE) by quantitative real-time PCR. SIRT1 and SIRT7 protein expression was evaluated by immunohistochemistry using Allred score. Compared to NNE, ECs showed SIRT7 (p < 0.001) mRNA overexpression, whereas SIRT1 (p < 0.001), SIRT2 (p < 0.001), SIRT4 (p < 0.001) and SIRT5 (p < 0.001) were underexpressed. No significant differences were observed for SIRT3 and SIRT6. Type II ECs displayed lower SIRT1 (p = 0.032) and SIRT3 (p = 0.016) transcript levels than Type I ECs. Concerning protein expression, SIRT1 immunostaining median score was higher in ECs compared to NNE epithelium (EC = 5 vs. NNE = 2, p < 0.001), while SIRT7 was lower in ECs (EC = 6 vs. NNE = 7, p < 0.001). No significant associations were found between SIRT1/7 immunoexpression and histological subtype, grade, lymphovascular invasion or stage. Our data shows that sirtuins are deregulated in EC. The diversity of expression patterns observed suggests that sirtuins may have distinctive roles in endometrial cancer similarly to what has been described in other cancer models.

CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas.

The clinicopathological significance of amplification was investigated of the gene encoding cyclin E (CCNE1) and we assessed whether CCNE1 was a potential target in endometrioid endometrial carcinomas. CCNE1 amplification and CCNE1 or F-box and WD repeat domain-containing 7 (FBXW7) expression in endometrial endometrioid carcinoma was assessed by immunohistochemistry and fluorescence in situ hybridization. CCNE1 knockdown by small interfering RNA (siRNA) was used to assess the CCNE1 function. The results showed that CCNE1 amplification was present in 9 (8.3%) of 108 endometrial carcinomas. CCNE1 amplification was correlated with high histological grade (Grade 3; P=0.0087) and lymphovascular space invasion (P=0.0258). No significant association was observed between CCNE1 amplification and FIGO stage (P=0.851), lymph node metastasis (P=0.078), body mass index (P=0.265), deep myometrial invasion (P=0.256), menopausal status (P=0.289) or patient age (P=0.0817). CCNE1 amplification was significantly correlated with shorter progression-free and overall survival (P=0.0081 and 0.0073, respectively). CCNE1 protein expression or loss of FBXW7 expression in endometrial endometrioid carcinoma tended to be correlated with shorter progression-free and overall survival; however, this difference was not statistically significant. Multivariate analysis showed that CCNE1 amplification was an independent prognostic factor for overall survival but not for progression-free survival (P=0.0454 and 0.2175, respectively). Profound growth inhibition was observed in siRNA-transfected cancer cells with endogenous CCNE1 overexpression compared with that in cancer cells having low CCNE1 expression. CCNE1 amplification was independent of p53, HER2, MLH1 and ARID1A expression but dependent on PTEN expression in endometrial carcinomas. These findings indicated that CCNE1 amplification was critical for the survival of endometrial endometrioid carcinomas. Furthermore, the effects of CCNE1 knockdown were dependent on the CCNE1 expression status, suggesting that CCNE1-targeted therapy may be beneficial for patients with endometrial endometrioid carcinoma having CCNE1 amplification.

Intact PTEN Expression by Immunohistochemistry is Associated With Decreased Survival in Advanced Stage Ovarian/Primary Peritoneal High-grade Serous Carcinoma.

Ovarian high-grade serous carcinoma is an aggressive malignancy with poor prognosis. Optimal surgical debulking and tumor sensitivity to platinum-based chemotherapy are 2 well-established prognostics for this tumor type. Molecular markers that identify more clinically aggressive tumors would potentially allow for the development of individualized treatment options. PTEN is a key negative regulator of the PI3K signaling pathway. Loss of PTEN expression in endometrial carcinoma is associated with endometrioid histology; women with endometrioid tumors have a better prognosis than those with nonendometrioid tumors. The prognostic and predictive value for PTEN has not been effectively explored in ovarian/peritoneal high-grade serous carcinoma. PTEN immunohistochemistry was assessed in 126 women with Stage III, high-grade serous carcinoma of the ovary/peritoneum treated with surgery and then a platinum-based regimen. Compared with PTEN-negative or PTEN-reduced tumors, positive PTEN immunohistochemistry, detected in 58% of tumors, was associated with decreased pS6 and increased PTEN mRNA levels. Positive PTEN expression was independent of surgical debulking status or platinum sensitivity. PTEN-positive tumors were associated with significantly decreased recurrence-free survival. Importantly, the devised PTEN immunohistochemistry scoring system was reproducible among pathologists.

Abrupt loss of MLH1 and PMS2 expression in endometrial carcinoma: molecular and morphologic analysis of 6 cases.

Given that endometrial cancer (EC) is often the sentinel cancer for female Lynch syndrome patients, we have successfully implemented universal screening of ECs and have previously shown that this is the preferred method to identify these patients. However, during the course of universal screening of EC, we encountered 6 cases with an unusual pattern of mismatch-repair protein immunohistochemistry that has not been previously described in this setting. In these 6 cases, there was an abrupt loss of MLH1 and PMS2 expression in a portion of the tumor. In 3 cases, marked histologic differences were identified between the areas of the tumor with retained expression and areas with loss of expression. In 2 cases, the areas with loss of expression were of higher grade (1 demonstrated solid growth and the other demonstrated increased nuclear atypia with diffuse p53 expression). In 4 tumors, histologic features associated with microsatellite instability (MSI) were present, including increased intraepithelial lymphocytes. The areas with loss of and retained MLH1/PMS2 expression were separately microdissected and assessed for MSI and MLH1 promoter methylation. The areas with loss of MLH1 and PMS2 more commonly demonstrated MSI compared with the areas with intact expression (83% vs. 33%). MLH1 promoter methylation analysis demonstrated heterogenous hypermethylation, as all areas with loss of MLH1/PMS2 expression had more extensive methylation of MLH1 compared with those areas with retained expression. In summary, we describe the histologic and molecular features of 6 cases of EC with abrupt loss of MLH1 and PMS2 expression and demonstrate that heterogenous methylation of the MLH1 promoter results in this distinct and unusual pattern of immunohistochemical expression.

Overexpression of ANCCA/ATAD2 in endometrial carcinoma and its correlation with tumor progression and poor prognosis

This study aimed to explore the clinical significance of AAA+ (ATPases associated with various cellular activities) nuclear coregulator cancer-associated (ANCCA) protein expression in endometrial carcinoma (EC). Correlations of ANCCA expression with clinicopathological factors and prognosis of EC patients were analyzed. Expression of ANCCA was detected in EC from 207 patients along with corresponding normal endometrium specimens by immunohistochemistry. ANCCA immunoreactivity was overexpressed in EC cases compared with that in normal endometrium (P < 0.001). High ANCCA expression was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, depth of myometrial invasion, lymph node metastasis, lymph vascular space involvement, and recurrence but not with age and histological type. Patients with high ANCCA expression exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than patients with low ANCCA expression (P = 0.001 and 0.002, respectively). Cox multivariate analysis showed that high ANCCA expression was an independent prognostic factor for both OS (hazard ratio (HR) = 4.954, 95 % confidence interval (CI) = 1.537-15.966; P = 0.007) and DFS of patients with EC (HR = 4.237, 95 % CI = 1.295-13.859; P = 0.017). We identified ANCCA protein expression as a novel independent poor prognostic indicator in EC.

Clinical significance of Sam68 expression in endometrial carcinoma.

Sam68 (Src-associated in mitosis of 68 kDa) is a substrate for tyrosine kinase c-Src during mitosis. The nuclear protein level has been found to be associated with progression and prognosis in various human malignant tumors. The aim of this study is to investigate the clinical value of Sam68 in endometrial carcinoma (EC). Sam68 expression was confirmed by real-time PCR, Western blot, and immunofluorescent assay in primary normal endometrial epithelial cells, endometrial carcinoma cell lines, as well as seven pairs of EC and matched adjacent noncancerous endometrial tissues. Moreover, the protein level of Sam68 was evaluated by immunohistochemistry in a cohort of surgical specimens derived from 131 patients including primary endometrial carcinoma (n = 95), endometrial atypical hyperplasia (precancerous lesions, n = 26), and normal endometria (n = 10). In endometrial cancer cell lines, RNA interfering approach was employed to downregulate Sam68 expression to determine its role in proliferation. Clinicopathological relevance and prognostic associations were examined by statistical analyses. Compared with normal endometrial and endometrial atypical hyperplasia tissues, Sam68 significantly elevated in endometrial cancer samples (P < 0.01), which was negative or low in 37 cases (38.9 %) and high in 58 cases (61.1 %). The high expression of Sam68 was associated with histological grade (P < 0.001), FIGO stage (P = 0.039), and myometrial invasion (P = 0.002). Kaplan-Meier analysis demonstrated that overexpression of Sam68 correlated with shorter overall survival. It is confirmed by univariate and multivariate analysis (P < 0.001 and P = 0.048, respectively). Additionally, we found that Sam68 was highly expressed at both the transcriptional and translational levels in endometrial cancer cell lines (Ishikawa, HEC-1B, AN3CA, KLE, and RL95-2) and siRNA knockdown of Sam68 remarkably inhibited cellular proliferation in in vitro models. Sam68 may be useful prognostic marker for EC, and it plays an important role in promoting the cellular proliferation. Further investigation of Sam68 as a potential therapeutic target for EC patients could be of interest.

Expression of the ELAV-like protein HuR in the cytoplasm is associated with endometrial carcinoma progression

Human antigen R (HuR) is an mRNA-binding factor that belongs to the embryonic lethal abnormal vision/Hu protein family which may function as a tumor maintenance gene in a variety of carcinomas. However, there is no study to analyze HuR expression in endometrial carcinoma. Here, we investigated the expression of HuR in endometrial carcinoma carcinogenesis and subsequent progression. The expression of HuR and estrogen receptor alpha (ER-α) protein was examined by immunohistochemistry on paraffin embedding specimens containing endometrial carcinoma and adjacent non-cancerous tissues. Short hairpin RNA against HuR was transfected to investigate the role of HuR in regulating the expression of ER-α and progression in endometrial carcinoma. Cell viability and cycle were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. Apoptosis was examined by annexin V apoptosis assay. Our study result show that cytoplasmic HuR expression is more frequent in poorly differentiated carcinomas (p = 0.005), advanced stage (p = 0.020), and positive ER-α expression (p = 0.026). Three HuR short hairpin RNAs (shRNAs) were transfected into Ishikawa cells, and we selected the most effective shRNA for the following experiments. After the transfection, the ER-α protein level was decreased. Further, decreased expression of HuR resulted in the inhibition of proliferation and induced apoptosis in Ishikawa cells. Our results showed that HuR could be a causal factor of ER-α regulation in Ishikawa cells and thus may induce the hormone-dependent endometrial carcinoma.

Expression and clinical significance of FXYD3 in endometrial cancer.

FXYD3 expression is upregulated in numerous cancer cell types. The present study compared the FXDY3 expression in normal endometrium, premalignant lesion and endometrial cancer tissue samples, and investigated the correlation between FXDY3 expression and clinicopathological features. FXYD3 expression was analyzed by streptavidin-peroxidase immunohistochemistry in 21 normal endometrial tissue samples, 18 atypical endometrial hyperplasia samples and 50 tissues obtained from patients diagnosed with endometrial cancer. The percentage of FXYD3-positive cell expression in the normal endometrium, atypical hyperplasia and endometrial cancer tissues samples was 0, 22, and 26%, respectively. The differences between the atypical hyperplasia and endometrial cancer groups were statistically significant when compared with the normal group (P=0.007 and P=0.037, respectively). There was no significant difference between the atypical hyperplasia and endometrial cancer groups. The percentage of FXYD3-positive cells correlated with the fertility frequency (P<0.05). In conclusion, FXYD3 is a potential biomarker for endometrial cancer, and its upregulation may be an early event in endometrial carcinoma progression. In addition, FXYD3 expression in endometrial carcinoma correlates with fertility frequency.

Aberrant MicroRNA Expression in Endometrial Carcinoma Using Formalin-Fixed Paraffin-Embedded (FFPE) Tissues

This study aimed to identify the candidate miRNAs in the carcinogenesis of endometrial carcinoma, and to explore whether FFPE material would be suitable for miRNA profiling. We identified the differences between miRNA expression profiles using human miRNA microarray in endometrioid endometrial adenocarcinomas (EECs) and normal endometria. Of those tested, miR-200a*, miR-200b*, miR-141, miR-182, and miR-205 were greatly enriched. The expressions of these five miRNAs were validated using quantitative real-time reverse transcription-PCR (qRT-PCR). We then performed qRT-PCR miR expression profiling in 30 FFPE specimens (20 EECs, 10 normal endometria) and re-confirmed the results of differential expression between cancer and normal tissue. Following this, we tested whether the specific inhibition of overexpressed miRNAs would alter chemosensitivity. In the in vitro cell viability assay, anti-miR200b* showed a trend toward enhanced cytotoxicity slightly in cisplatin compared to the negative control (p = 0.07). This information provided the candidate miRNAs for further confirmation of the role of miRNAs in the carcinogenesis of EECs, potentially serving as a diagnostic or therapeutic tool. FFPE specimens of endometrial tissues are suitable as a source for miRNA microarray profiling.

Ras-induced Up-regulation of CTP:Phosphocholine Cytidylyltransferase α Contributes to Malignant Transformation of Intestinal Epithelial Cells

Cancer cells have enhanced lipogenic capacity characterized by increased synthesis of fatty acids and complex lipids, including phosphatidylcholine (PC). As the rate-limiting enzyme in the CDP-choline pathway for PC synthesis, CTP:phosphocholine cytidylyltransferase α (CCTα) is implicated in the provision of membranes and bioactive lipids necessary of cell proliferation. In this study, we assessed the role of CCTα in malignant intestinal epithelial cells transformed with activated H-ras (IEC-ras). Three IEC-ras clones had significant up-regulation CCTα expression, but PC synthesis and in vitro activity of CCTα were similar to control IEC. RNA interference of CCTα in adherent IEC-ras did not affect PC synthesis, confirming that the enzyme was relatively inactive. However, CCTα silencing in ras-transformed IEC reduced anchorage-independent growth, a criterion for malignant transformation, as well as tumorigenicity in mice. Relative to their adherent counterparts, detached IEC-ras had increased PC synthesis that was attenuated by inducible CCTα silencing. Detachment of IEC-ras was accompanied by increased CCTα phosphorylation and cytosolic enzyme activity. We conclude that the expanded pool of CCTα in IEC-ras is activated by detachment. This provides the increased PC biosynthetic capacity that contributes to malignant transformation of intestinal epithelial cells when detached from the extracellular matrix.

DNMT Inhibitors and HDAC Inhibitors Regulate E-Cadherin and Bcl-2 Expression in Endometrial Carcinoma in vitro and in vivo

Background: The effect of histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors (DNMTIs) on proliferation of endometrial cancer (EC) cells in vitro and in vivo was investigated. Methods: Changes in methylation of the CDH1 promoter in HDACI- and DNMTI-treated HEC-1-B and RL-952 EC cells were detected. Nude mice with xenografted implants of human EC HEC-1-B cells were treated with valproic acid (VPA) and decitabine (DAC) and evaluated for tumor growth, CDH1 and Bcl-2 mRNA levels. Results: DAC, VPA and suberoylanilide hydroxamic acid (SAHA) inhibited proliferation, induced cell cycle arrest and enhanced the apoptotic index in both cell lines, DAC, VPA and SAHA upregulated E-cadherin mRNA and protein levels and downregulated Bcl-2 mRNA levels in vitro. DAC and VPA inhibited tumor growth, upregulated CDH1 mRNA and downregulated Bcl-2 mRNA levels in vivo. Conclusions: A combination of HDACIs and DNMTIs suppresses the growth of EC, which is likely mediated by upregulation of E-cadherin and downregulation of Bcl-2.

Tumor budding and E-Cadherin expression in endometrial carcinoma: Are they prognostic factors in endometrial cancer?

ObjectiveTo evaluate the prognostic value of tumor budding (TB) in endometrioid (EEC) and non-endometrioid endometrial cancers (NEEC) and to determine its correlation with expression of E-cadherin. MethodsNinety-five patients with primary endometrial carcinoma were examined statistically. All patients were diagnosed, treated, and given follow-up care at Dokuz Eylul University Faculty of Medicine. Tumor budding detected by either H&E-stained sections and anticytokeratin-staining C11. The tissue block with the largest invasive front was chosen for budding counting and immunostaining. E-cadherin expression was examined by immunohistochemistry using the primary antibodies against to it. ResultsTumor budding was low-grade in 73 and high-grade in 22 cases. E-cadherin expression loss was identified in 48 patients. The high-grade TB was significantly higher in patients with advanced stage and deep myometrial invasion (p=0.032 and 0.018, respectively). E-Cadherin expression was significantly lower in NEECs than EECs (p=0.032). The negative expression of E-cadherin was associated with advanced stage and poor differentiation (p=0.001 and p=0.024, respectively). We determined that tumor budding adversely correlated with the presence of E-cadherin expression but not statistically significant. Based on the results of multivariate analysis, TB has an independent impact on cumulative overall survival. We found no statistically significant difference between E-cadherin expression and survival. ConclusionsTB is associated with undifferentiated tumor, advanced stage and decreased postoperative survival in endometrial cancer. It might be a valuable prognostic clinicopathologic factor which can be applicable in routine examination.

Analysis of the expression of angiotensin II type 1 receptor and VEGF in endometrial adenocarcinoma with different clinicopathological characteristics

In Poland, endometrial carcinoma takes second place after breast cancer among all cancers in women and is considered the most common genital cancer. It has been repeatedly reported that angiotensin is involved in the development and invasion of some cancers including breast, ovarian, and pancreatic ones. It is suggested that angiotensin two and its receptors are actively involved in tumour biology in endometrial adenocarcinoma. In the present study, we identify a possible relationship between the expression of AT1-R, AT2-R, ERα, and VEGF and clinicopathological characteristics of primary endometrial adenocarcinoma. We determined the above components both at the mRNA (real-time RT-PCR) and protein levels (Western Blot assay). Our results indicate that in patients with grade G3 adenocarcinoma, the expression of AT1-R significantly decreased in comparison with G1 patients (p = 0.034), but the level of ERα was the highest in G2 and the lowest in G3. Moreover, the level of VEGF mRNA significantly increased between G2 and G3 (p = 0.034). We also noted a significant correlation between the expression of AT1-R and AT2-R in FIGO stage 1 (R (s) = 0.9636; p = 0.0001) and that of AT2-R and VEGF (R (s) = 0.5377; p = 0.005). In grade G1 and G2 carcinoma, a significant correlation was also found between the expression of AT1-R and AT2-R (R (s) = 0.9924; p = 0.0001; R (s) = 0.8717, p = 0.0005, respectively), but in grade G1, a negative correlation was observed between AT1-R and VEGF (R (s) = -0.8945, p = 0.0005). Further studies are required to clarify the biological function of the angiotensin receptor in regulating VEGF expression in endometrial carcinoma.