ABSTRACT
This study aimed to assess the expression profile of messenger RNA (mRNA) and microRNA (miRNA) related to the dopaminergic system in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B (n = 196, including HER2-, n = 100; HER2+, n = 96), HER2+ (n = 36), and TNBC (n = 43); they underwent surgery, during which tumor tissue was removed along with a margin of healthy tissue (control material). The molecular analysis included a microarray profile of mRNAs and miRNAs associated with the dopaminergic system, a real-time polymerase chain reaction preceded by reverse transcription for selected genes, and determinations of their concentration using enzyme-linked immunosorbent assay (ELISA). The conducted statistical analysis showed that five mRNAs statistically significantly differentiated breast cancer sections regardless of subtype compared to control samples; these were dopamine receptor 2 (DRD2), dopamine receptor 3 (DRD3), dopamine receptor 25 (DRD5), transforming growth factor beta 2 (TGF-ß-2), and caveolin 2 (CAV2). The predicted analysis showed that hsa-miR-141-3p can regulate the expression of DRD2 and TGF-ß-2, whereas hsa-miR-4441 is potentially engaged in the expression regulation of DRD3 and DRD5. In addition, the expression pattern of DRD5 mRNA can also be regulated by has-miR-16-5p. The overexpression of DRD2 and DRD3, with concomitant silencing of DRD5 expression, confirms the presence of dopaminergic abnormalities in breast cancer patients. Moreover, these abnormalities may be the result of miR-141-3P, miR-16-5p, and miR-4441 activity, regulating proliferation or metastasis.
Subject(s)
Breast Neoplasms , Dopamine , Gene Expression Regulation, Neoplastic , MicroRNAs , Humans , Female , MicroRNAs/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Middle Aged , Dopamine/metabolism , Adult , Gene Expression Profiling/methods , Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Dopamine D3/genetics , Receptors, Dopamine D3/metabolism , Receptors, Dopamine D2/genetics , Receptors, Dopamine D2/metabolism , Transforming Growth Factor beta2/genetics , Transforming Growth Factor beta2/metabolismABSTRACT
The purpose of this study was to evaluate the relationship between human papillomavirus (HPV16/18), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) infections and the occurrence of ovarian cancer in 48 women, of whom 36 underwent surgery and chemotherapy (group A), 12 in whom surgery was sufficient (group B), and 60 with endometroid endometrial cancer stage G1-G3 (group C), compared to patients in whom the uterus and its appendages were removed for nononcological reasons (control group). The detection of HPV, EBV, and HCMV in tumor tissue and normal tissue was performed using the real-time polymerase chain reaction (RT-PCR) technique. A statistically significantly higher risk of endometrial cancer was noted in patients infected only with HCMV (OR > 1; p < 0.05). In contrast, a significantly higher risk of ovarian cancer in group A was associated with HPV16, HPV18, and EBV (OR > 1; p < 0.05); a significantly higher risk of ovarian cancer in group B was associated with HPV18 and HMCV (OR > 1; p < 0.05). The obtained results suggest that HCMV infection is associated with the development of a stage of ovarian cancer when treatment can be completed with surgery alone. Meanwhile, EBV appears to be responsible for the development of ovarian cancer in more advanced stages.
ABSTRACT
PURPOSE: Changes in the activity of endothelins and their receptors may promote neoplastic processes. They can be caused by epigenetic modifications and modulators, but little is known about endothelin-3 (EDN3), particularly in endometrial cancer. The aim of the study was to determine the expression profile of endothelin family and their interactions with miRNAs, and to assess the degree of EDN3 methylation. METHODS: The study enrolled 45 patients with endometrioid endometrial cancer and 30 patients without neoplastic changes. The expression profile of endothelins and their receptors was determined with mRNA microarrays and RT-qPCR. The miRNA prediction was based on the miRNA microarray experiment and the mirDB tool. The degree of EDN3 methylation was assessed by MSP. RESULTS: EDN1 and EDNRA were overexpressed regardless of endometrial cancer grade, which may be due to the lack of regulatory effect of miR-130a-3p and miR-485-3p, respectively. In addition, EDN3 and EDNRB were significantly downregulated. CONCLUSION: The endothelial axis is disturbed in endometrioid endometrial cancer. The observed silencing of EDN3 activity may be mainly due to DNA methylation.
Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , MicroRNAs , Female , Humans , Endothelin-3/genetics , Endothelin-3/metabolism , Endothelins/genetics , Endothelins/metabolism , MicroRNAs/genetics , Receptor, Endothelin A/genetics , Endometrial Neoplasms/genetics , Carcinoma, Endometrioid/genetics , Gene Expression Regulation, Neoplastic , Endothelin-1/genetics , Endothelin-1/metabolismABSTRACT
Reactive oxygen species are formed as by-products of normal cell metabolism. They are needed to maintain cell homeostasis and signaling, which is possible due to defense systems. Disruption of this balance leads to oxidative stress that can induce cancer. Redox regulation by miRNAs may be a potential therapeutic target. The aim of the study was to assess the activity of genes associated with oxidative stress in endometrial cancer and to determine their relationship with miRNAs. The study included 45 patients with endometrioid endometrial cancer and 45 without neoplastic changes. The expression profile of genes associated with oxidative stress was determined with mRNA microarrays, RT-qPCR and ELISA. The miRNA prediction was performed based on the miRNA microarray experiment and the mirDB tool. PRDX2 and AQP1 showed overexpression that was probably not related to miRNA activity. A high level of PKD2 may be the result of a decrease in the activity of miR-195-3p, miR-20a, miR-134. A SOD3 level reduction can be caused by miR-328, miR-363. In addition, miR-363 can also regulate KLF2 expression. In the course of endometrial cancer, the phenomenon of oxidative stress is observed, the regulation of which may be influenced by miRNAs.
Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , MicroRNAs , Female , Humans , MicroRNAs/metabolism , Carcinoma, Endometrioid/genetics , Endometrial Neoplasms/genetics , Oxidative Stress/genetics , Gene Expression , Gene Expression Regulation, Neoplastic , Gene Expression ProfilingABSTRACT
It is estimated that more and more couples suffer from fertility and pregnancy maintenance disorders. It is associated with impaired androgen secretion, which is influenced by many factors, ranging from genetic to environmental. It is also important to remember that fertility disorders can also result from abnormal anatomy of the reproductive male and female organ (congenital uterine anomalies - septate, unicornuate, bicornuate uterus; acquired defects of the uterus structure - fibroids, polyps, hypertrophy), disturbed hormonal cycle and obstruction of the fallopian tubes resulting from the presence of adhesions due to inflammation, endometriosis, and surgery, abnormal rhythm of menstrual bleeding, the abnormal concentration of hormones. There are many relationships between the endocrine organs, leading to a chain reaction when one of them fails to function properly. Conditions in which the immune system is involved, including infections and autoimmune diseases, also affect fertility. The form of treatment depends on infertility duration and the patient's age. It includes ovulation stimulation with clomiphene citrate or gonadotropins, metformin use, and weight loss interventions. Since so many different factors affect fertility, it is important to correctly diagnose what is causing the problem and to modify the treatment regimen if necessary. This review describes disturbances in the hormone secretion of individual endocrine organs in the context of fertility and the maintenance of pregnancy.
Subject(s)
Endocrine System Diseases , Infertility , Leiomyoma , Pregnancy , Male , Female , Humans , Fertility , Reproduction , Uterus , Clomiphene , Endocrine System Diseases/complications , Endocrine System Diseases/therapyABSTRACT
INTRODUCTION: The aim of the study was to identify predictors of surgical complications of transurethral resection of bladder tumour (TURBT). MATERIAL AND METHODS: We prospectively recruited 983 consecutive patients undergoing TURBT within 7 months in six academic institutions. All patients were followed up from the surgery up to 30 days postoperatively with at least one telephone contact at the end of the observation. The primary study endpoint was any intra- or postoperative surgical complication. For the identification of predictors of complications, univariate and multivariate logistic regression models were used. Trial registration: ClinicalTrials.gov (NCT03029663). Registered 24 January 2017. RESULTS: Surgical complications were noticed in 228 (23.2%) patients, including 83 (8.4%) patients with more than one complication and 33 cases of Clavien-Dindo grade 3 complications (3.3%). The most common in-hospital complications were bleeding (n = 139, 14.1%) and bladder perforation (n = 46, 4.7%). In a multivariate analysis, nicotine use, high ASA score, and the presence of high-grade tumour were the most significant predictors of high-grade complications. The stage of the disease was the strongest predictor of bleeding, while the presence of muscle in the specimen and resident surgeon were the strongest predictors for bladder perforation. CONCLUSIONS: TURBT poses a significant risk of surgical complications, the majority of which are of low grade.
ABSTRACT
AIM: Receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) is responsible for induction of selective immunosuppression. In addition, preclinical studies have shown that sRCAS1 levels may reflect cancer aggressiveness. The main aim of our study was to analyze pre- and post-treatment levels of sRCAS1 in the sera of patients treated for cervical cancer and to evaluate whether the levels change during treatment and their impact on patient prognosis. METHODS: The study included 49 patients suffering from cervical cancer. The early stage cervical cancer patients (14) were treated surgically, while the advanced stage patients (35) underwent radiochemotherapy. Serum sRCAS1 levels were evaluated both before and after intervention with the use of the ELISA method. RESULTS: We have found that median serum sRCAS1 levels of patients before intervention were not significantly different from the levels assessed after intervention. There were also no differences when pre- and post-treatment levels were compared within the group of early and of advanced stage patients. Serum sRCAS1 levels were not influenced by either the histopathological type of the tumor or the methods of treatment. High post-intervention sRCAS1 levels indicated shortened OS when compared to low sRCAS1 levels. Neither pre-intervention sRCAS1 levels nor the alteration in sRCAS1 levels during treatment were associated with patient prognosis. In multivariate analysis, post-treatment sRCAS1 levels and clinical stage of cervical cancer remained as independent predictors of survival. CONCLUSION: High post-treatment serum sRCAS1 level in cervical cancer patients seems to be a negative prognostic factor for patient overall survival.
Subject(s)
Adenocarcinoma/mortality , Antigens, Neoplasm/blood , Carcinoma, Squamous Cell/mortality , Uterine Cervical Neoplasms/mortality , Adenocarcinoma/blood , Adenocarcinoma/therapy , Adult , Aged , Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Female , Gynecologic Surgical Procedures , Humans , Middle Aged , Prognosis , Survival Rate , Uterine Cervical Neoplasms/blood , Uterine Cervical Neoplasms/therapyABSTRACT
BACKGROUND: Endometrial cancer is one of the most common gynecological cancer in the developed countries and occurs mainly in postmenopausal women. Angiogenesis is important for cancer formation as it provides nutrients for growing tumor mass. Most tumors do not show detectable Homeobox A5 (HOXA5 level), suggesting its potential role as a cancer suppressor. It was demonstrated that HOXA5 is involved in the progression of various types of cancer and the loss of its expression correlates with higher pathological grade and poorer outcome. OBJECTIVE: The aim of the study was to evaluate HOXA5 expression at transcriptome and protein levels. MATERIALS AND METHODS: The study enrolled 45 women diagnosed with endometrial cancer and 15 without neoplastic changes. The histopathological examination allowed us to divide cancer tissue samples according to the degree of histological differentiation: G1, 17; G2, 15; G3, 13. The expression of the HOXA5 protein was determined by immunohistochemistry. Microarray and RT-qPCR techniques were used to assess HOXA5 expression at the mRNA level. RESULTS: The reaction to the HOXA5 protein was only visible in glandular cells in G1 endometrial cancer and was lower compared to the control. In grades 2 and 3, reactions were noted at the limit of the method's sensitivity. In addition, reduced HOXA5 expression was observed at the transcriptome level. CONCLUSION: HOXA5 may become a potential complementary molecular marker, allowing early detection of neoplastic changes in the endometrium. It also seems that detection of HOXA5 at the mRNA and protein levels may be helpful in improving the accuracy of diagnosis and planning effective oncological therapy.
Subject(s)
Endometrial Neoplasms/metabolism , Homeodomain Proteins/metabolism , Neovascularization, Pathologic/metabolism , Transcription, Genetic , Cell Differentiation/genetics , Endometrial Neoplasms/blood supply , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Homeodomain Proteins/genetics , Humans , Immunohistochemistry , Middle Aged , Neovascularization, Pathologic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
BACKGROUND: Many experimental studies have demonstrated the importance of COX-2 in the tumor angiogenesis. Inducible iNOS is responsible for a high and stable level of nitric oxide and is expressed in response to pro-inflammatory factors. OBJECTIVE: The aim of this study was to evaluate the expression of COX-2 and iNOS at the protein level and to assess their potential prognostic significance in patients with endometrial cancer. METHODS: The study group consisted of 45 women with endometrial cancer divided according to the degree of histological differentiation i.e. G1, 17; G2, 15; G3, 13. The control group consisted of 15 women without neoplastic changes. The expression of studied proteins was determined immunohistochemically with specific polyclonal antibodies. RESULTS: Analysis of the COX-2 expression showed that the optical density of the reaction product in G1 reached 186% in the control group, while the values in G2 and G3 reached 243% and 293%, respectively. In the case of iNOS, the optical density of the reaction product reached the following percentages in the control group: 147% in G1, 243% in G2, and 241% in G3. CONCLUSION: Our findings suggest that changes in the expression of COX-2 and iNOS may be potentially useful in predicting the progression of endometrial cancer and treatment effectiveness.
Subject(s)
Cyclooxygenase 2/metabolism , Endometrial Neoplasms/metabolism , Nitric Oxide Synthase Type II/metabolism , Aged , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Grading , PrognosisABSTRACT
BACKGROUND: Semaphorin 5A (SEMA5A) functions not only in the nervous system but also in cancer transformation where its role has not yet been sufficiently studied and described. OBJECTIVE: The aim of the study was to determine the changes in SEMA5A expression in endometrial cancer at various degrees of its differentiation (G1-G3) compared to control. MATERIALS AND METHODS: The study group consisted of 45 patients with endometrial cancer at various grades: G1, 17; G2, 15; G3, 13. The control consisted of 15 women without neoplastic changes in the routine gynecological examination. The statistical analysis of immunohistochemical assessment of SEMA5A level was carried out using the Statistica 12 program based on the Kruskal-Wallis test and Dunn's post-hoc test (p<0.05). RESULTS: The expression of SEMA5A (optical density) was observed in the control group (Me = 103.43) and in the study group (G1, Me = 140.72; G2, Me = 150.88; G3, Me = 173.77). Differences in expression between each grade and control and between individual grades turned out to be statistically significant (p<0.01). The protein level of SEMA5A expression increased with the decreasing degree of endometrial cancer differentiation. CONCLUSION: In our research, we indicated the overexpression of SEMA5A protein in endometrial cancer. It is a valuable starting point for further consideration of the role of SEMA5A as a new supplementary molecular marker in endometrial cancer.
Subject(s)
Biomarkers, Tumor/metabolism , Endometrial Neoplasms/metabolism , Semaphorins/metabolism , Cell Differentiation , Endometrial Neoplasms/pathology , Endometrium/metabolism , Female , HumansABSTRACT
BACKGROUND: Vascular endothelial growth factor (VEGF)-C, -D, and VEGF receptor-3 are proteins characterized as crucial for tumor lymphangiogenesis. It is accompanied by angiogenesis during wound healing, but also in the neoplastic process. The research studies have shown that the lymphatic system plays a key role in the progression of carcinogenesis. OBJECTIVE: The aim of this study was to evaluate changes in the expression of VEGF-C, VEGF-D and VEGFR-3 in different grades of endometrial cancer (G1-G3). METHODS: The study included 45 patients diagnosed with endometrial cancer (G1=17; G2=15; G3=13) and 15 patients without neoplastic changes. The expression of VEGF-C, VEGF-D, and VEGFR-3 was assessed using microarray technique and immunohistochemistry. Statistical analysis was performed using the one-way ANOVA and Tukey's post-hoc test. RESULTS: Statistically significant changes in the expression at the transcriptome level were found only in the case of VEGF-C (G1 vs. C, fold change - FC = -1.15; G2 vs. C, FC = -2.33; G3 vs. C, FC = - 1.68). However, VEGF-D and VEGFR-3 were expressed at the protein level. Analysis of VEGF-D expression showed that the optical density of the reaction product in G1 reached 101.7, while the values in G2 and G3 were 142.7 and 184.4, respectively. For VEGF-R3, the optical density of the reaction product reached the following levels: 72 in control, 118.77 in G1, 145.8 in G2, and 170.9 in G3. CONCLUSION: An increase in VEGF-D and VEGFR-3 levels may indicate that VEGF-D-dependent processes are intensified along with the dedifferentiation of tumor cells. The lack of VEGF-C expression in endometrial cancer samples may suggest that this tumor is characterized by a different mechanism of metastasis than EMT. Our study emphasizes that when analyzing the metastatic potential of cancer, the expression of more than one factor should be taken into account.
Subject(s)
Endometrial Neoplasms/genetics , Neovascularization, Pathologic/genetics , Vascular Endothelial Growth Factor C/genetics , Vascular Endothelial Growth Factor D/genetics , Vascular Endothelial Growth Factor Receptor-3/genetics , Endometrial Neoplasms/pathology , Female , Humans , Immunohistochemistry , Lymphangiogenesis/genetics , Neoplasm GradingABSTRACT
BACKGROUND: VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 are important proteins involved in the induction and development of a new blood vessel network through which the tumor is properly nourished and oxygenated. OBJECTIVES: The aim of the study was to evaluate changes in VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 expression in endometrial cancer depending on its grade and to determine the VEGFR-1 to VEGFR-2 concentration ratio. METHODS: The study group consisted of 45 patients diagnosed with endometrial cancer (G1, 17; G2, 15; G3, 13). The control group included 15 patients. VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 expression was assessed using the immunohistochemical method. Statistical analysis was carried out using the Statistica 12 PL program (StatSoft, Cracow, Poland). It included the one-way ANOVA and Tukey's post-hoc test (p<0.05). RESULTS: Statistically significant differences in the level of VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 were observed between the majority of analyzed groups (except for VEGF-B; G3 vs. G1, p=0.997700). The expression pattern of VEGF-A, VEGF-R1, VEGFR-2 was as follows: G3>G2>G1>C; VEGF-B: G2> G3> G1>C. A lower concentration of VEGFR-1 than VEGFR-2 was found regardless of the cancer grade. CONCLUSION: VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 are key proteins involved in tumor angiogenesis. The analysis of the entire panel of proteins participating in a given process is an important element of modern diagnostics. The concentration ratio of VEGFR-1 to VEGFR-2 appears to be a determining factor in the patients' survival prognosis.
Subject(s)
Endometrial Neoplasms/metabolism , Neovascularization, Pathologic/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor B/metabolism , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Case-Control Studies , Endometrial Neoplasms/blood supply , Endometrial Neoplasms/pathology , Female , Humans , Immunohistochemistry , Neoplasm Grading , Prognosis , RNA, Messenger/metabolismABSTRACT
BACKGROUND SEMA3B is known as an inhibitor of angiogenesis and cell proliferation. During carcinogenesis, the loss of SEMA3B function is observed, which results in the progression of neoplastic changes. The aim of this study was to evaluate the expression profile of SEMA3B in endometrial cancer (G1-G3) in comparison to the control group and to assess whether the observed changes in expression could become a molecular marker in endometrial cancer. MATERIAL AND METHODS The study group consisted of 45 patients diagnosed with endometrial cancer (G1, 17; G2, 15; G3, 13). The control group included 15 patients. SEMA3B expression was assessed using the immunohistochemical method. Statistical analysis was carried out using the Statistica 12 PL program (StatSoft, USA). It included the Kruskal-Wallis test and post hoc Dunn's test (p<0.05). RESULTS Statistically significant differences in the level of SEMA3B expression were observed between all analyzed groups. The expression pattern of SEMA3B was as follows: cancer cells G1>G2>G3; endothelial cells: G3>G1>G2; stromal cells: G2>G1>G3. CONCLUSIONS Analysis of the SEMA3B expression profile shows the complexity of neoplastic transformation, which confirms the different expression of SEMA3B in endometrial cancer cells and endothelial cells. The present results and data in the literature data suggest that SEMA3B expression indicates the progression of carcinogenesis in the context of endometrial cancer.
Subject(s)
Endometrial Neoplasms/genetics , Membrane Glycoproteins/genetics , Semaphorins/genetics , Adult , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Transformation, Neoplastic , Endometrial Neoplasms/metabolism , Endometrium/metabolism , Endothelial Cells/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/genetics , Humans , Membrane Glycoproteins/metabolism , Neoplasm Staging , Neovascularization, Pathologic/metabolism , Semaphorins/metabolism , Signal Transduction/drug effects , Transcriptome/geneticsABSTRACT
BACKGROUND: In the course of neoplastic diseases, a reduction in SEMA3F expression is observed, which translates into an increase in the proliferative and proangiogenic potential of cells forming the tumor and the surrounding microenvironment. OBJECTIVE: The aim of this study was to determine the changes in SEMA3F level in endometrial cancer depending on its grade. METHODS: The study material consisted of tissue samples: 15 without neoplastic changes (control group) and 45 with endometrial cancer (G1, 17; G2, 15; G3, 13; study group). SEMA3F expression was assessed using the immune-histochemical method. RESULTS: The expression of SEMA3F was observed in the control group (Me = 159.38) and in the study group (G1, Me = 121.32; G2, Me = 0; G3, Me = 130.37). Differences between each grade and control and between individual grades were statistically significant. There were no significant correlations between SEMA3F expression and weight and Body Mass Index (BMI). The reduced SEMA3F expression in tumor tissue compared to healthy tissue indicates that this protein plays key roles in proliferation and angiogenesis. CONCLUSION: We found that depending on the severity of the disease, cancer adopts different survival strategies, where SEMA3F plays an important role. As a molecular marker, SEMA3F is not sensitive to weight and BMI.
Subject(s)
Endometrial Neoplasms/metabolism , Membrane Proteins/metabolism , Neovascularization, Pathologic/metabolism , Nerve Tissue Proteins/metabolism , Case-Control Studies , Endometrial Neoplasms/blood supply , Endometrial Neoplasms/pathology , Female , Humans , Immunohistochemistry , Neoplasm Grading , Pilot Projects , Tumor Microenvironment/drug effectsABSTRACT
OBJECTIVES: There is growing evidence that Treg cell infiltration into the cancer nest is associated with poor prognosis. How- ever, the Treg cell population in the peripheral blood may change when a different type of anticancer therapy is applied. Since Treg cells may support tumor growth by enhancing the suppressive profile of the cancer microenvironment, the assessment of Treg cells can bring to light important information regarding prognosis. Thus we decided to analyze the Treg cell population in the peripheral blood in relation to long-term outcomes in the group of patients with ovarian cancer. MATERIAL AND METHODS: The 80 patients included in the study were treated surgically followed by chemiotherapy for ovar- ian cancer between October 2010 through May 2011.The peripheral blood samples from the patients were collected directly prior to chemotherapy. Information on any patients who died was retrieved from the database of the Cuiavia-Pomerania Regional Office of the National Health System of Poland. CD4+CD25+FOXP3+ lymphocytes T were assed by flow cytometry. We have analyzed the long term outcomes of treatment regarding to the level of Treg cells in peripheral blood. RESULTS: We found that patients with serous adenocarcinomas had significantly higher Treg levels compared to those patients with non-serous types. Patients who had a higher percentage of Treg cells within the CD4+ cell population prior to the beginning of the treatment had worse long-term outcomes from the applied therapy. CONCLUSIONS: The assessment of Treg levels prior to the start of chemotherapy is clinically useful and may predict overall survival in ovarian cancer patients.
Subject(s)
Ovarian Neoplasms/immunology , Ovarian Neoplasms/mortality , T-Lymphocytes, Regulatory/immunology , Adult , Aged , Aged, 80 and over , Female , Flow Cytometry , Follow-Up Studies , Humans , Middle Aged , Ovarian Neoplasms/blood , Ovarian Neoplasms/therapy , Poland , Survival Analysis , T-Lymphocytes, Regulatory/cytology , Treatment OutcomeABSTRACT
BACKGROUND: EDIL3 is an extracellular matrix protein that plays a key role in angiogenesis. Changes in the pattern of its expression also affect cellular processes and the tumor microenvironment. Elevated level of EDIL3 is considered an unfavorable prognostic marker of survival. OBJECTIVE: The aim of this study was to evaluate the changes in EDIL3 expression in endometrial cancer at various degrees of its differentiation (G1-G3) and to discuss its potential role as a molecular diagnostic marker and therapeutic target. METHODS: The study group consisted of 45 patients with endometrial cancer: G1, 17; G2, 15; G3, 13. The control group (C) included 15 patients without neoplastic changes. The expression of EDIL3 was assessed using immunohistochemistry. Statistical analysis was performed using the Statistica 12 PL software (p<0.05). RESULTS: Analysis of EDIL3 expression showed that the average optical density of the reaction product in G1 reached 130% of the control, while the values in G2 and G3 were 153% and 158%, respectively. Regardless of the endometrial cancer grade, an increase in EDIL3 level was observed compared to the control. CONCLUSION: In our study, we demonstrated overexpression of EDIL3 protein in endometrial cancer. Differences in expression between degrees of tumor differentiation suggest the potential of using changes in EDIL3 level as a new complementary diagnostic marker and target for anti-angiogenic therapy.
Subject(s)
Biomarkers, Tumor/metabolism , Carrier Proteins/metabolism , Endometrial Neoplasms/metabolism , Neovascularization, Pathologic/metabolism , Calcium-Binding Proteins , Case-Control Studies , Cell Adhesion Molecules , Cell Differentiation , Endometrial Neoplasms/pathology , Female , Humans , Immunohistochemistry , Middle Aged , Neoplasm Grading , Neovascularization, Pathologic/pathology , Tumor MicroenvironmentABSTRACT
BACKGROUND: Neuropilins (NRPs) participate in many processes related to cancer development such as angiogenesis, lymphangiogenesis and metastasis. Although endometrial cancer is one of the most common gynecological cancers, it has not been studied in terms of NRPs expression. OBJECTIVE: The aim of this study was to investigate the potential utility of NRPs as important factors in the diagnosis and treatment of endometrial cancer. METHODS: Our study consisted of 45 women diagnosed with endometrial cancer at the following degrees of histological differentiation: G1, 17; G2, 15; G3, 13 cases. The control group included 15 women without neoplastic changes. The immunohistochemical reactions were evaluated using light microscopy. RESULTS: We did not detect the expression of NRP-1 and NRP-2 in the control group. NRP-1 expression was found exclusively in cancer cells. It was higher in G2 and G3 and reached about 190% of G1. NRP-2 expression was observed in the endothelium and was similar across all three cancer grades. In cancer cells, NRP-2 expression increased with the degree of histological differentiation. CONCLUSION: NRP1 and NRP2 are candidates for complementary diagnostic molecular markers and promising new targets for molecular, personalized anticancer therapies.
Subject(s)
Biomarkers, Tumor/biosynthesis , Endometrial Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Neuropilin-1/biosynthesis , Neuropilin-2/biosynthesis , Biomarkers, Tumor/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Female , Humans , Hysterectomy , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/surgery , Neuropilin-1/genetics , Neuropilin-2/genetics , Tumor Cells, CulturedABSTRACT
PROBLEM: Aberrant expression of human leukocyte antigen-G (HLA-G) in various malignancies has been shown to participate in tumour development by suppressing immune regulation within the tumour microenvironment. The detection of HLA-G has reportedly been correlated with certain clinicopathological parameters in several neoplasms. Both the soluble and membranous forms of HLA-G are biologically active, and therefore, we aimed to evaluate the HLA-G level by Western blot technique. METHOD OF STUDY: The total amount of HLA-G protein was analyzed in the primary tumour in 113 tissue samples derived from patients with endometrial cancer. The HLA-G protein level was measured by Western Blot technique and was analyzed with respect to the clinicopathological parameters. RESULTS: Human leukocyte antigen-G protein levels were statistically significantly higher in the cancerous tissues derived from the women with advanced endometrial cancer than those from women with early stage disease. Moreover, we showed that endometrial cancer patients with lymph node metastases had statistically significantly higher HLA-G levels in the primary uterine tumour. CONCLUSION: The aberrant expression of HLA-G antigens by malignant cells could be one of the strategies tumour cells use to escape immune surveillance. The presence of HLA-G within the cancer nest and its microenvironment would seem to be linked to disease progression.
Subject(s)
Biomarkers, Tumor/metabolism , Blotting, Western/methods , Endometrial Neoplasms/diagnosis , HLA-G Antigens/metabolism , Histocompatibility Testing/methods , Adult , Aged , Aged, 80 and over , Disease Progression , Endometrial Neoplasms/pathology , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Tumor MicroenvironmentABSTRACT
Objectives The aim of our study has been to determine the association between the appearance of infection after modified posterior pelvic exenteration (MPE) and TTC (time to adjuvant chemotherapy) and to examine whether the infection impacts clinical results by delaying the start of chemotherapy. Material and methods The present, retrospective study analyzed 77 patients who had undergone MPE followed by adjuvant chemotherapy. Either no residual tumor or tumor less than 2.5 mm was achieved in 76.7% of these patients. Patients were divided into two subgroups for comparison; the first group consisted of 41 patients with infections, the second group of 36 patients without infections. Infection after surgery was monitored within a 90-day postoperative period. Median TTC and OS (overall survival) was determined for those patients who developed infection as well as for those who did not. Results The expected 5-year survival rate was 0.40 (SD=0.09) for those patients without infection and 0.17 (SD=0.07) for those patients with infection. The survival curves of patients with infection and those without infection were statistically significantly different (p=0.038). Median TTC differed significantly for those patients who developed infection vs those patients who did not develop infection (37days vs 27.5 days, p=0.024), and patients without infection were statistically more likely to receive chemotherapy within 25 days following surgery than in the subsequent 25-42-day period compared to those patients who did develop infection (p=0.048). No statistically significant differences were found between the groups in relation to the initiation of chemotherapy within 42 days (p=0.445). Conclusions The absence of postoperative infection was associated with a better survival. Patients with infection were noted a longer time interval from surgery to start of chemotherapy without negative impact to OS.
Subject(s)
Bacteremia/epidemiology , Chemotherapy, Adjuvant/statistics & numerical data , Ovarian Neoplasms/surgery , Pelvic Exenteration , Surgical Wound Infection/epidemiology , Survival Rate , Time-to-Treatment/statistics & numerical data , Urinary Tract Infections/epidemiology , Adult , Aged , Colectomy , Colostomy , Cytoreduction Surgical Procedures , Digestive System Surgical Procedures , Female , Humans , Hysterectomy , Ileostomy , Intestine, Small/surgery , Middle Aged , Neoplasm Grading , Neoplasm Staging , Omentum/surgery , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Rectum/surgery , Retrospective Studies , Salpingo-oophorectomy , SplenectomyABSTRACT
BACKGROUND: Endoglin is a marker of active, proliferating endothelial cells of blood vessels. In many cancers, it is present in both peripheral vessels and vessels located inside the tumor. Endoglin is more specific and sensitive compared to other tumor angiogenesis markers. It is suggested that endoglin can be considered a reliable marker of disease outcome. OBJECTIVE: The aim of the study was to assess the expression of endoglin and to determine its potential usefulness as a complementary molecular marker of endometrial cancer. METHOD: The study included 60 women who underwent hysterectomy: 45 with endometrioid endometrial cancer (study group) and 15 without neoplastic changes (control group). The study group was further divided according to the degree of histological differentiation: G1, 17; G2, 15; and G3, 13. The expression of endoglin was determined immunohistochemically with mouse anti-Endoglin monoclonal antibody. The obtained reactions were evaluated using light microscopy. RESULTS: Analysis of endoglin expression in endothelium showed that it reached 145% of the control. In G2, we observed that the endoglin level decreased and was similar to the control, while in G3 it increased and was even higher than in G1. In cancer cells, endoglin expression increased with the grade of endometrial cancer. CONCLUSION: Endoglin can be considered a valuable complementary molecular marker, allowing to visualize the advancement of the cancer process, including endometrial cancer.