RESUMEN
The PI3K/AKT pathway is frequently activated in endometrial carcinoma. BMI-1 (B-lymphoma Mo-MLV insertion region 1) protein affects expression of PTEN (phosphatase and tensin homolog) in some cancers, but its significance for endometrial tumorigenesis is not known. The objective of this study was to determine the relationship between BMI-1 and expression of factors affecting AKT (protein kinase B) phosphorylation level in endometrial cancer. The expression of proteins and mRNAs was investigated in endometrial cancer specimens and samples of non-neoplastic endometrial tissue by Western blot and RT-PCR, respectively. The impact of BMI-1 down-regulation on AKT phosphorylation and expression of genes coding for several phosphatases were studied in HEC1A cells. The results showed that BMI-1 depletion caused increase in PHLPP1 and PHLPP2 (PH domain and leucine-rich repeat protein phosphatases 1/2) expression and decrease in phospho-AKT (pAKT) level. In more advanced tumours with higher metastatic potential, the expression of BMI-1 was lower compared to tumours less advanced and without lymph node metastasis. There were significant inverse correlations between BMI-1 and PHLPPs, especially PHLPP1 in normal endometrial samples. The inverse correlation between BMI-1 and PHLPP1/PHLPP2 expression was observed in PTEN positive but not PTEN negative cancers. Low PHLPP2 expression in tumours predicted poorer overall survival. BMI-1 impacts on AKT phosphorylation level in endometrial cells by regulation of PHLPP expression.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Endometriales/patología , Proteínas Nucleares/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Complejo Represivo Polycomb 1/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Proliferación Celular , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas Nucleares/genética , Fosfohidrolasa PTEN/genética , Fosfoproteínas Fosfatasas/genética , Fosforilación , Complejo Represivo Polycomb 1/genética , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
The exchange of metabolites between mitochondria and cytosol occurs through pores formed by voltage-dependent anion channel proteins. Voltage-dependent anion channels appear to be master regulators of mitochondrial bioenergetics and the intracellular flow of energy. Deregulation of voltage-dependent anion channels expression is thought to be related to mitochondrial dysfunction in cancer. The aim of this study was to investigate the mRNA and protein expression levels of VDAC1, VDAC2, and VDAC3 in relation to clinicopathological characteristics of endometrial cancer as well as the prognostic significance of voltage-dependent anion channels expression for overall survival. VDAC1 and VDAC3 expressions were significantly higher in cancer compared to normal tissues. Kaplan-Meier analysis indicated that high expression of all VDAC genes or high VDAC2 protein level predicted poor overall survival. Multivariate analysis identified the VDAC1 and VDAC2 mRNA levels as well as VDAC2 protein level as independent prognostic factors. Our results suggest that increased expression of voltage-dependent anion channels correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.
Asunto(s)
Neoplasias Endometriales/patología , Mitocondrias/patología , Proteínas de Transporte de Membrana Mitocondrial/genética , Canal Aniónico 1 Dependiente del Voltaje/genética , Canal Aniónico 2 Dependiente del Voltaje/genética , Canales Aniónicos Dependientes del Voltaje/genética , Secuencia de Aminoácidos , Biomarcadores de Tumor/genética , Citoplasma/metabolismo , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Mitocondrias/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/biosíntesis , Pronóstico , ARN Mensajero/genética , Canal Aniónico 1 Dependiente del Voltaje/biosíntesis , Canal Aniónico 2 Dependiente del Voltaje/biosíntesis , Canales Aniónicos Dependientes del Voltaje/biosíntesisRESUMEN
OBJECTIVES: Endometrial cancer is the most common cancer of the female genital organs in developed countries, accounting for approximately 50% of all gynecological cancers. The Klotho gene was discovered in 1997 as an anti-aging gene that, when overexpressed, may extend the lifespan, but when disrupted, may be a factor responsible for premature aging syndrome. The aim of the study is to assess the relationship between the clinical and pathological features of endometrial cancer and ßKlotho gene expression. MATERIAL AND METHODS: The expression of ßKlotho gene was studied in 138 cases of endometrioid endometrial carcinoma specimens using Real Time PCR reaction in RNA isolated tissue samples by commercial tests. The expression profile was correlated with the clinicopathological characteristics of endometrial carcinoma. The chi-square independence test and Fisher's test for four-field tables were used to assess the statistical significance of the observed relationships. RESULTS: Significant relationships were found between ßKlotho gene expression and FIGO clinical stage, the degree of histological differentiation and the presence of metastases in the lymph nodes. Higher levels of gene expression correlate with lower degrees of clinical staging according to FIGO, the presence of highly-differentiated endometrial cancer (G1) and the absence of lymph node metastases. CONCLUSIONS: The ßKlotho gene expression might be involved in endometrioid endometrial cancer tumorgenesis. The ßKlotho may in future be used as an useful indicator for endometrial cancer, although further studies are needed.
Asunto(s)
Carcinoma Endometrioide/genética , Neoplasias Endometriales/genética , Proteínas de la Membrana/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto , Femenino , Expresión Génica , Humanos , Proteínas Klotho , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
Ten-eleven translocation proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine, and 5-carboxylcytosine that play a significant role in DNA demethylation. Deregulation of TET genes expression and changes in the level of 5-hmC are thought to be associated with the onset and progression of several types of cancer, but there are no such data related to endometrial cancer. The aim of the work was to investigate the messenger RNA expression levels of TET1, TET2, and TET3 in relation to clinicopathological characteristics of endometrial cancer as well as the correlation between expression of TET genes and the level of 5-hmC/5-mC. The prognostic significance of TETs expression for overall survival was established. We found that TET1 and TET2 messenger RNA expression was lower and TET3 was higher in cancers compared to normal tissues. Positive correlation between 5-hmC and the relative expression of TET1 and TET2 was found, but no correlation was observed in the case of TET3. Decreased expression of TET1 and TET2 was significantly associated with increased lymph node metastasis and International Federation of Gynecology and Obstetrics stage. Kaplan-Meier analysis indicated that low TET1 expression predicted poor overall survival (p = 0.038). Multivariate analysis identified the TET1 expression in endometrial cancer as an independent prognostic factor. Our results suggest that decreased expression of TET1 correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.
Asunto(s)
Metilación de ADN/genética , Proteínas de Unión al ADN/biosíntesis , Dioxigenasas/biosíntesis , Neoplasias Endometriales/genética , Oxigenasas de Función Mixta/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Anciano , Citosina/análogos & derivados , Citosina/metabolismo , Proteínas de Unión al ADN/genética , Dioxigenasas/genética , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Oxigenasas de Función Mixta/genética , Pronóstico , Proteínas Proto-Oncogénicas/genéticaRESUMEN
OBJECTIVES: The aim of the study was to evaluate the cytotoxic effect of metformin on the ovarian cancer cells SKOV-3 and analyze the impact of this compound on the expression of genes coding for O-GlcNAc cycling enzymes, i.e. O-GlcNAc transferase (OGT) and -N-acetylglucosaminidase (OGA). MATERIALS AND METHODS: Viability and proliferation of control cells and cells treated with metformin were evaluated by MTT test and trypan blue staining. OGT and OGA mRNA expressions analysis was performed using real-time PCR method. RESULTS: A metformin concentration-dependent decrease of SKOV-3 cell viability was observed. The IC50 parameter for metformin cytotoxicity was 14 mM. The SKOV-3 cell doubling time was 45 hours. The cell population treated with 10 mM metformin did not double even after 72 hours. There was no significant difference in mRNA level of OGA between control cells and cells treated with metformin. The OGT mRNA level was significantly higher in cells treated with metforrhin for 24 hours as compared to the control cells. The increase of OGT mRNA was dependent on time of incubation. Cells treated with metformin for 48 hour showed higher expression of OGT than cells treated for 24 hours. CONCLUSION: Antiproliferative activity of metformin suggests that this compound may be considered as a candidate for potential chemotherapeutic agent. However taking into account its impact on the expression of O-GlcNAc transferase, further studies on the molecular mechanism of metformin action are necessary
Asunto(s)
Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Metformina/farmacología , N-Acetilglucosaminiltransferasas/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , beta-N-Acetilhexosaminidasas/genética , beta-N-Acetilhexosaminidasas/metabolismo , Adulto , Antineoplásicos/farmacología , Línea Celular/efectos de los fármacos , Citotoxinas/farmacología , Femenino , Humanos , Concentración 50 Inhibidora , N-Acetilglucosaminiltransferasas/genética , Neoplasias Ováricas/patologíaRESUMEN
PURPOSE: Angiogenesis, a multistep process that results in new blood vessel formation from preexisting vasculature is essential for both the growth of solid tumour and for metastasis. Stimulation of vascular endothelial growth factor receptor (VEGFR), a transmembrane glycoprotein, results in mitogenesis. Within this family of receptors, VEGFR 2/kinase-insert-domain containing receptor appears to be principally upregulated during tumorigenesis. The aim of this study was to determine the expression of VEGFR-2/kinase-insert-domain containing receptor (KDR) and its correlation with angiotensin receptor type 1 (AT1-R) and clinical factors in endometrial carcinoma. METHODS: The expression of KDR and AT1-R was studied in endometrial carcinoma and normal endometrium by Real-time RT-PCR and Western blot analysis in 136 samples. The expression profile was correlated with the clinicopathological characteristics of endometrial adenocarcinoma. RESULTS: We noted a significant correlation between the expression of KDR and AT1-R in tumour grade G1, G2 and G3 (R(s)=0.50; p=0.002, R(s)=0.69; p=0.0001, R(s)=0.52; p=0.005, respectively). In stage I and stage II carcinoma, a significant correlation was also found between the expression of KDR and AT1-R (R(s)=0.70, p=0.0001, R(s)=0.67; p=0.001, respectively). Moreover significant correlation was observed between both KDR and AT1-R in tissue with different myometrial invasion (R(s)=0.54, p=0.0001, R(s)=0.68; p=0.0001; respectively for tumours with invasion into the inner half and invasion into the outer half). CONCLUSIONS: Basing on received correlation between AT1-R and KDR expression and previous results we speculate that angiotensin through AT1-R modulates KDR expression and thus have influence on local VEGF level. However, further studies are required to clarify the biological interaction between KDR, AT1-R and other hormonal regulators in endometrial carcinoma.
Asunto(s)
Neoplasias Endometriales/genética , Regulación Neoplásica de la Expresión Génica , Receptor de Angiotensina Tipo 1/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Breast cancer is the most common malignancy in women. Its estimated annual incidence is about one million cases worldwide. A number of risk factor have been identified, among them early menarche, late menopause, nulliparity and positive family history Moreover a number of highly penetrant breast and ovarian cancer susceptibility genes, such as BRCA 1 and BRCA2, have been identified. Recent findings suggest TopBP1 to be a breast and ovarian cancer susceptibility gene. Moreover; TopBPI protein may be an important prognostic marker of breast cancer TopBP1 protein is involved in DNA replication, mitosis and meiosis, as well as DNA repair Deregulation of these processes may have pathological implications in cancer
Asunto(s)
Neoplasias de la Mama/genética , Proteínas Portadoras/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad/genética , Proteínas Nucleares/genética , Neoplasias Ováricas/genética , Femenino , Humanos , Mutación/genética , Factores de Riesgo , Salud de la MujerRESUMEN
OBJECTIVES: The metastatic ability of tumors is characteristic for malignant neoplasms and constitutes the main cause of therapeutics failures. Metastasis formation involves the sequence of processes such as proteolytic degradation of the basement membrane, migration, intravasation, extravasation, proliferation and angiogenesis. Cadherins and integrins are groups of proteins directly involved in these processes. In the present study we analyzed the mRNA expression of CDH1 and ITGB1 genes by real-time polymerase chain reaction (RT-PCR). The study included 106 endometrial carcinomas. CDH1 and ITGB1 mRNA expression was found in all of the studied samples. Generally the CDH1 and ITGB1 mRNA expression was significantly higher in well-differentiated rather than poorly differentiated tumors. MATERIALS AND METHODS: The mRNA expression levels of CDH1 and ITGB1 in series of 83 samples of endometrial carcinoma were studied by real time RT-PCR method. Statistical analysis of the obtained results was performed. RESULTS: CDH1 and ITGB1 gene expression was observed in all examined tissues and was correlated with cancer malignancy (G). In high grade malignant tumors (G1), CDH1 and ITGB1 gene expression was the highest, in G2 and G3 tumors the expression of both genes was gradually lowering. Moreover the statistically significant correlation between CDH1 and ITGB1 gene expression was observed. (Spearman test, r=0.29, pAsunto(s)
Cadherinas/genética
, Neoplasias Endometriales/genética
, Regulación Neoplásica de la Expresión Génica
, Integrina beta1/genética
, ARN Mensajero/genética
, Neoplasias del Cuello Uterino/genética
, Antígenos CD
, Neoplasias Endometriales/patología
, Femenino
, Humanos
, Reacción en Cadena de la Polimerasa
, Neoplasias del Cuello Uterino/patología
RESUMEN
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.
Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/patología , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Receptor de Angiotensina Tipo 1/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adenocarcinoma/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Expresión Génica , Humanos , Persona de Mediana Edad , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/genética , Receptor de Angiotensina Tipo 2/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Breast and ovarian cancer are among the most common malignancies of women in the world. About 5 - 10% of the cases are considered familial. Germline mutations in the BRCA1 and BRCA2 genes are strong predictors of breast and/or ovarian cancer development. However currently known susceptibility genes including BRCA1, BRCA2, ATM, Chk2, PALB2, and BRIP1 explain less than 25% of familial breast and/ovarian cancers. Other genes, such as TopBP1 are also likely to be involved in hereditary predisposition to breast and/or ovarian cancer TopBP1 protein displays structural and functional similarities with BRCA1, and these two proteins have been suggested to function partially in the same cellular processes. TopBP1 protein is involved in DNA repair and cell cycle checkpoint control. Moreover TopBP1 interacts with transcription factors, such as E2F1, p53, Miz-1, HPV16 E2, and regulates their activity.
Asunto(s)
Neoplasias de la Mama/genética , Proteínas Portadoras/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad/genética , Proteínas Nucleares/genética , Neoplasias Ováricas/genética , Análisis Mutacional de ADN , Femenino , Humanos , Mutación/genética , Factores de RiesgoRESUMEN
OBJECTIVES: O-GlcNAcylation is an abundant modification of cellular proteins which consist of single N-acetylglucosamine residues attached by O-linkage to serine or threonine residues. Abnormal O-GlcNAcylation seems to be a feature of malignant cancer cells. The aim of the present study was to determine the relationship between the expression of genes encoding O-GlcNAc cycling enzymes (OGT and MGEAS) and clinicopathological parameters of endometrial carcinomas. MATERIALS AND METHODS: The mRNA expression levels of O-GlcNAc cycling enzymes in series of 76 samples of endometrial carcinoma were studied by real time RT-PCR method. RESULTS: The OGT and MGEA5 mRNA expression was significantly higher in tumors of higher histological grade than in well-differentiated tumors. Statistically significant association was found between OGT and MGEA5 mRNA expression and depth of myometrial invasion. Both OGT and MGEA5 expression profiles showed no significant association with the clinical stage of endometrial cancer. CONCLUSION: O-GlcNAcylation may be an important regulatory modification involved in endometrial cancer pathogenesis but the actual significance of this modification for endometrial cancer progression needs to be investigated further.
Asunto(s)
Neoplasias Endometriales/enzimología , Neoplasias Endometriales/genética , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , beta-N-Acetilhexosaminidasas/genética , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Clasificación del TumorRESUMEN
We investigated single nucleotide polymorphism (SNP) of the betaglycan gene (TGFBR3) encoding the TGFß co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and gene expression were analyzed using TaqMan probes. Three out of the eight SNPs tested, i.e., rs12566180 (CT; OR = 2.22; 95% CI = 1.15-4.30; p = 0.0177), rs6680463 (GC; OR = 2.34; 95% CI = 1.20-4.53; p = 0.0120) and rs2296621 (TT; OR = 6.40; 95% CI = 1.18-34.84; p = 0.0317) were found to be significantly associated with increased risk of EC (adjusted to age, body mass index, menarche and parity). Among the analyzed SNPs, only rs2296621 demonstrated the impact on the increased cancer aggressiveness evaluated by the WHO grading system (G3 vs. G1/2, GT-OR = 4.04; 95% CI = 1.56-10.51; p = 0.0026; T-OR = 2.38; 95% CI = 1.16-4.85; p = 0.0151). Linkage disequilibrium (LD) analysis revealed high LD (r2 ≥ 0.8) in two haploblocks, constructed by rs2770186/rs12141128 and rs12566180/rs6680463, respectively. In the case of C/C haplotype (OR = 4.82; 95% CI = 1.54-15.07; p = 0.0116-Bonferroni corrected) and T/G haplotype (OR = 3.25; 95% CI = 1.29-8.15; p = 0.0328-Bonferroni corrected) in haploblock rs12566180/rs6680463, significantly higher frequency was observed in patients with EC as compared to the control group. The genotype-phenotype studies showed that SNPs of the TGFBR3 gene associated with an increased risk of EC, i.e., rs12566180 and rs2296621 may affect betaglycan expression at the transcriptomic level (rs12566180-CC vs. TT, p < 0.01; rs2296621-GG vs. TT, p < 0.001, GT vs. TT, p < 0.05). Functional consequences of evaluated TGFBR3 gene SNPs were supported by RegulomeDB search. In conclusion, polymorphism of the TGFBR3 gene may be associated with an increased EC occurrence, as well as may be the molecular mechanism responsible for observed betaglycan down-regulation in EC patients.
RESUMEN
INTRODUCTION: Malignant neoplasm of the endometrium is the most common malignant neoplasm of the female reproductive system. Toll Like Receptors (TLR) play a significant role in innate and late-immunity against infections or damaged tissues. TLRs are also involved in the development of tumors in their natural microenvironment. TLRs play an important role in angiogenesis, necessary for survival and growth of the tumor. Hypoxia playing a critical role in angiogenesis, carcinogenesis, tumor progression and distant metastasis is primarily mediated through hypoxia inducible factors (HIFs). Vascular endothelial growth factor family proteins (VEGF) are also strongly involved in tumor angiogenesis and their action is strongly associated with TLR receptors. OBJECTIVES: The aim of the study was to correlate the expression of selected TLRs and VEGFR's as well as HIF1α with clinicopathological data of endometrial cancer patients. MATERIAL AND METHODS: 123 neoplastic endometrial samples were included in the study. 51 samples of healthy endometrium served as control. The expression of TLR1, TLR2, TLR3, TLR4, VEGFR1 and VEGFR2, VEGF-A and HIF1α was examined after RNA isolation at the mRNA level by Real Time-PCR. RESULTS: We have noted a significant correlation between the expression of selected TLR and VEGFR's and clinical stage as well as pathological grading of endometrial cancer. CONCLUSIONS: Received correlations confirm a significant contribution of some TLR expression and the receptor for VEGF in the pathogenesis of epithelial endometrial cancer.
Asunto(s)
Neoplasias Endometriales/metabolismo , Endometrio/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Transducción de Señal/fisiologíaRESUMEN
OBJECTIVES: The aim of the study was to assess the correlation between the activity of thymidine phosphorylase (TP) and the platelet derived-endothelial cell growth factor (PD-ECGF) expression in endometrial carcinoma. METHODS: The study group consisted of 40 tissue samples taken from patients with endometrial carcinoma, who underwent surgery in First Clinic of Gynecology and Oncologic Gynecology of Medical University in Lodz. The control tissue samples were taken from patients who were operated on for non-oncologic reason. The activity of TP was measured by the spectrophotometric method in the cytosol of tumor cells, and the immunohistochemical staining of PD-ECGF was performed in the same tumors. The results of TP activity were compared with the microvessel density (MD) assessed by immunohistochemical analysis and with clinico-pathological features like tumor grade and FIGO stage. RESULT: A positive correlation between the enzyme activity and expression of TP/PD-ECGF protein was found. Moreover a significantly higher TP activity was confirmed in malignant tumors from endometrial cancer patients when compared to the controls. A positive correlation between the enzyme activity and MD was also stated, but there was no connection to the grade of tumors and FIGO stage. Since the TP activity proved to be related to PD-ECGF expression and angiogenesis, we can state that TP seems to be an active form of PD-ECGF growth factor in endometrial carcinoma. This is in agreement with the results of many publications on other malignancies. The proper modulation of this activity may be useful in adjuvant therapies.
Asunto(s)
Neoplasias Endometriales/enzimología , Timidina Fosforilasa/biosíntesis , Timidina Fosforilasa/metabolismo , Femenino , Humanos , Inmunohistoquímica , EspectrofotometríaRESUMEN
OBJECTIVES: Endometrial cancers (ECs) are the most common gynaecological cancers in well developed countries. Diabetes and metabolic syndrome are among the biggest risk factors. Nesfatin-1, the adipokine derivative of NUCB2 (nucleobindin derivative 2) is linked to the clinical course of EC. Molecular factors, including mutations in MLH1 and MHS2 genes, c-MET and ARID1A are also related to prognosis in endometrial cancer. MATERIAL AND METHODS: Using sections of paraffin-embedded preparations and immunohistochemistry, the expression of NESF1, MLH1, MSH2,c-MET and ARID1A were examined. RESULTS: In this study on protein expression, EC tissues manifested (although insignificantly) an elevated expression of NESF-1 in type II EC. In type I EC, NESF-1 expression was significantly higher in G1 in comparison to G2 and G3 together. A significantly lower expression of MLH1 was demonstrated in type I EC. CONCLUSIONS: The most pronounced expression involved c-MET in all EC I and EC II tissues (in over 80% of cases). A tendency was detected for a high expression of NESF-1 in patients with type II EC, who also exhibited a high expression of MSH2.
Asunto(s)
Neoplasias Endometriales/clasificación , Neoplasias Endometriales/metabolismo , Nucleobindinas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Proteínas de Unión al ADN/análisis , Proteínas de Unión al ADN/metabolismo , Neoplasias Endometriales/química , Neoplasias Endometriales/diagnóstico , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Nucleobindinas/análisis , Pronóstico , Estudios Retrospectivos , Factores de Transcripción/análisis , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Endometrial carcinomas (EC) differ in etiology, clinical course and prognosis. OBJECTIVES: This multi-center study aimed at a closer recognition of molecular factors linked to heterogeneity of EC by evaluating estrogen and progesterone receptors, proteins dependent on MMR genes, proteins linked to poor prognosis and metastases, and mutations in BRCA1. MATERIAL AND METHODS: Using sections of paraffin-embedded preparations, in 115 patients with EC type I and 31 with EC type II, expression of ERα, ERß1, PR, MLH1, and MSH2 proteins, as well as ARID1A, c-MET and BRCA1, was estimated by immunohistochemistry using specific antibodies. RESULTS: Expression of ERß1 was augmented in EC type II, in poorly differentiated cancers and with growing clinical advancement. An augmented expression of ERα was noted in well-differentiated EC and at lower clinical stage. An increased expression of PR and decreased of MLH1 were detected in type I EC. The expression of ARID1A and c-MET proteins showed no differences between the types of EC, stages of clinical advancement or grading. In 51.6% patients with type II EC, a loss of BRCA1 expression was disclosed; in this group of cancers a decreased expression of ERα was noted. CONCLUSIONS: An augmented expression of ERß1 was linked to type II EC. A higher expression of ERα in EC cancers was associated with a lower histopathological grade. A decreased expression of MLH1 protein was estimated in EC type I. Type II EC may be connected to BRCA1 mutation.
Asunto(s)
Proteína BRCA1/genética , Neoplasias Endometriales/metabolismo , Homólogo 1 de la Proteína MutL/genética , Homólogo 1 de la Proteína MutL/metabolismo , Receptores de Estrógenos/genética , Receptores de Progesterona/genética , Carcinoma Endometrioide/patología , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Genes BRCA1 , Humanos , Inmunohistoquímica , Mutación , Pronóstico , Regiones Promotoras Genéticas/genéticaRESUMEN
This study defines the role of WWOX in the regulation of epithelial to mesenchymal transition. A group of 164 endometrial adenocarcinoma patients was studied as well as an ECC1 well-differentiated steroid-responsive endometrial cell line, which was transducted with WWOX cDNA by a retroviral system. The relationship between WWOX gene and EMT marker (CDH1, VIM, ZEB1, SNAI1) expression on mRNA (RT-qPCR) and protein levels (western blotting) was evaluated. The EMT processes were also analysed in vitro by adhesion of cells to extracellular matrix proteins, migration through a basement membrane, anchorage-independent growth and MMP activity assay. DNA microarrays (HumanOneArray™) were used to determine WWOX-dependent pathways in an ECC1 cell line. A positive correlation was observed between WWOX and ZEB1, and a negative correlation between CDH1 and VIM. WWOX expression was found to inversely correlate with the risk of recurrence of tumors in patients. However, in the WWOX-expressing ECC1 cell line, WWOX expression was found to be inversely related with VIM and positively with CDH1. The ECC1/WWOX cell line variant demonstrated increased migratory capacity, with increased expression of metalloproteinases MMP2/MMP9. However, these cells were not able to form colonies in suspension and revealed decreased adhesion to fibronectin and fibrinogen. Microarray analysis demonstrated that WWOX has an impact on the variety of cellular pathways including the cadherin and integrin signalling pathways. Our results suggest that the WWOX gene plays a role in the regulation of EMT processes in endometrial cancer by controlling the expression of proteins associated with cell motility, thus influencing tissue remodeling, with the suppression of mesenchymal markers.
Asunto(s)
Neoplasias Endometriales/patología , Transición Epitelial-Mesenquimal , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Antígenos CD , Cadherinas/genética , Cadherinas/metabolismo , Adhesión Celular , Línea Celular Tumoral , Movimiento Celular , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Vimentina/genética , Vimentina/metabolismo , Oxidorreductasa que Contiene Dominios WW , Homeobox 1 de Unión a la E-Box con Dedos de ZincRESUMEN
OBJECTIVE: to evaluate the relationship between AgNORs count as well as tumor grade and the effect of chemotherapy in serous ovarian cancer. MATERIAL AND METHODS: 39 women who underwent surgical procedure and then chemotherapy due to serous ovarian cancer were included into the study. In cancer cells the mean number of AgNORs per nucleus (mAgNOR) and the mean percentage of nuclei with five or more AgNORs (pAgNOR) were counted. RESULTS: in 13 women (33.3%) we did not found the neoplastic disease in second-look laparotomy (group I), and in 26 patients (66.7%) the cancer was present (group II). The mean grading and the mAgNOR of ovarian cancer in the first operation in group I and in group II were similar. The mean pAgNOR in group I was higher than in group II. The values of mAgNOR and pAgNOR but not grading in women with the absence of cancer in second-look laparotomy and in women with the only single neoplastic focuses were similar one to another, and both were higher than in cases of disseminated neoplastic disease. CONCLUSIONS: the quantitative assessment of AgNORs is better prognostic factor when compared to grading for the effectiveness of adjuvant chemotherapy in serous ovarian cancer.
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Cistadenocarcinoma Seroso/secundario , Estadificación de Neoplasias , Región Organizadora del Nucléolo/patología , Neoplasias Ováricas/patología , Adulto , Anciano , Núcleo Celular/patología , Quimioterapia Adyuvante , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/cirugía , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Pronóstico , Tinción con Nitrato de Plata , Resultado del TratamientoRESUMEN
Yolk sac tumor is the rare neoplasm, detected mostly in girls and young women above 30 yr. It is characterized by the high malignancy and short survival rate. We described the case of yolk sac tumor detected in 12-yrs old girl treated by combined method (nonradical tumor resection, chemotherapy, hysterectomy, bilateral adnexectomy and chemotherapy according to SFOP) and with the complete remission more than 1 year after the treatment was completed.
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Tumor del Seno Endodérmico , Neoplasias Pélvicas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Niño , Tumor del Seno Endodérmico/tratamiento farmacológico , Tumor del Seno Endodérmico/cirugía , Femenino , Humanos , Neoplasias Pélvicas/tratamiento farmacológico , Neoplasias Pélvicas/cirugía , Inducción de Remisión , Reoperación , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: In senium the increase in the incidence of most malignant neoplasms, as well as gynecological cancers is found. In this period of life the vast number of women do not apply for the preventive and follow-up examinations, which increases the number of malignant diseases diagnosed at advanced clinical stages. The coexisting another diseases often limits the possibility of the operative treatment in those cases. DESIGN: To assess the profile of malignant tumors of the genital tract and their treatment in women above 70 year old. MATERIAL AND METHODS: 61 women aged from 71 yrs. to 88 yrs. treated operatively between 1997-2001 due to gynecological cancers were included into the study. The structure and detectability of the neoplasms, as well as the type of performed surgical procedures were analysed. RESULTS: 30 endometrial cancers (49.2%), 16 ovarian cancers (26.2%), 14 vulvar cancers (22.9%) and 1 cervical cancer were diagnosed and surgically treated. The endometrial cancer stage I was detected in 18 cases, stage II in 4 cases and stage III in 8 cases. In each case the radical operation was done (total hysterectomy, lymphadenectomy and appendectomy). The ovarian cancer stage I was detected in 3 cases, stage II in 2 cases, stage III in 5 cases, and stage IV in 6 cases. Only in 5 cases out of this group the radical surgery was performed (total hysterectomy, omentectomy and appendectomy). The vulvar cancer stage I was detected in 2 cases, stage II in 11 cases, and FIGO stage III in 4 cases. In each of these women the vulva and bilateral inguinal lymph nodes were resected, and in 2 cases additionally at the same time the Miles operation was performed. The cervical cancer clinical stage I was detected, and the Wertheim operation was performed. CONCLUSIONS: The most often diagnosed malignant neoplasm in women above 70 yrs. was the endometrial cancer. The worst first-time diagnosis structure was observed in the ovarian cancer, what significantly decreased the ability of surgical treatment in this group.