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Liposarcomas are the most common soft tissue sarcoma in adults, whereas liposarcomas of the head and neck, particularly the hypopharynx, are incredibly rare - with approximately 50 cases reported in the literature. We present a case of an otherwise healthy and asymptomatic 42-year-old male who presented dramatically after vomiting up a large soft tissue mass. The lesion was surgically removed via transoral approach with blue laser, and diagnosis of well-differentiated liposarcoma was made via MDM2 gene amplification by FISH. Oral extrusion is a rare feature of this disease. This is the first documented case of an orally extruded liposarcoma to present in an otherwise asymptomatic and healthy patient, demonstrating how this entity may be indolent until initial presentation. Laryngoscope, 2024.
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INTRODUCTION: Parosteal osteosarcomas are low-grade bony malignancies that are treated primarily with surgical resection and reconstruction. This report discusses a unique case of a pediatric patient who presented with a parosteal osteosarcoma of the distal radius causing extensive erosive mass effect and growth disturbance of the adjacent ulna. Likely due to their slow-growing nonaggressive nature, parosteal osteosarcomas have not been previously described to abut adjacent bony structures through direct contact. The patient presented in a significantly delayed manner due to social circumstances, inadvertently revealing this novel behavior. This report reviews this rare case and describes the current understanding of this tumor. CASE PRESENTATION: The patient is a 13-year-old male who presented with a parosteal osteosarcoma of his distal radius. He presented with a palpable wrist mass and wrist stiffness. He presented in a delayed manner with advanced local disease due to social factors. Imaging revealed an osseous radial mass that abutted the ulna and likely stunted its growth. The patient ultimately underwent complex resection and allograft reconstruction of both his distal radius and ulna. Intraoperative pathology was confirmed to have negative tumor margins. Allograft reconstruction of the radius and ulna was performed utilizing patient-specific custom cutting guides. At the 6-month postoperative visit, the patient had no recurrence of the mass, minimal pain, and had almost regained range of motion of the extremities. Clinical radiographs at the 6-month postoperative visit demonstrated allograft incorporation. CONCLUSIONS: A previously unreported case of pediatric parosteal osteosarcoma of the distal radius with erosion of the adjacent ulna through direct contact is presented. The challenges in and the importance of arriving at a definitive diagnosis in a timely manner for the proper treatment of this malignancy are emphasized.
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Neoplasias Óseas , Osteosarcoma , Adolescente , Humanos , Masculino , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugía , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/cirugía , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/cirugía , Radio (Anatomía)/patología , Cúbito/diagnóstico por imagen , Cúbito/cirugía , Cúbito/patología , Extremidad Superior/patologíaRESUMEN
Liposarcoma is a carcinomatous mesenchymal tumor with various histologic features and is the most common soft tissue sarcoma originating in adipose tissue. Liposarcoma commonly occurs in the lower extremities and retroperitoneum but rarely in the mediastinum, specially extending into the thoracic cavity. We report a giant primary liposarcoma of the posterior mediastinum in a 63-year-old female who complained of cough, sputum, and pain in the right chest wall. A computed tomography scan of the chest showed a giant mass of 24 × 15 × 24 cm in the posterior mediastinum of the right thoracic cavity. After a thorough examination, no suspected lipomatous lesions were found elsewhere in the patient's body. The patient underwent a thoracotomy to remove the mediastinal mass through a right thoracic approach. Subsequently, hematoxylin-eosin staining revealed dedifferentiated liposarcoma (DDL), immunohistochemistry showed positive expression of cyclin-dependent kinase 4, and murine double minute 2 (MDM2), in addition, fluorescence in situ hybridization for the MDM2 gene was also positive, which suggested DDL. The patient was discharged without any complications, and no metastasis or recurrence was observed after 19 months of follow-up. To provide a reference for clinical diagnosis and treatment, we reviewed and discussed the literature on primary liposarcoma of the mediastinum.
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An evaluation of the expression and predictive significance of the MDM2 gene in brain lower-grade glioma (LGG) cancer was carried out using onco-informatics pipelines. Several transcriptome servers were used to measure the differential expression of the targeted MDM2 gene and search mutations and copy number variations. GENT2, Gene Expression Profiling Interactive Analysis, Onco-Lnc, and PrognoScan were used to figure out the survival rate of LGG cancer patients. The protein-protein interaction networks between MDM2 gene and its co-expressed genes were constructed by Gene-MANIA tool. Identified bioactive phytochemicals were evaluated through molecular docking using Schrödinger Suite Software, with the MDM2 (PDB ID: 1RV1) target. Protein-ligand interactions were observed with key residues of the macromolecular target. A molecular dynamics simulation of the novel bioactive compounds with the targeted protein was performed. Phytochemicals targeting MDM2 protein, such as Taxifolin and (-)-Epicatechin, have been shown with more highly stable results as compared to the control drug, and hence, concluded that phytochemicals with bioactive potential might be alternative therapeutic options for the management of LGG patients. Our once informatics-based designed pipeline has indicated that the MDM2 gene may have been a predictive biomarker for LGG cancer and selected phytochemicals possessed outstanding interaction results within the macromolecular target's active site after utilizing in silico approaches. In vitro and in vivo experiments are recommended to confirm these outcomes.
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Neoplasias Encefálicas , Glioma , Humanos , Proteína p53 Supresora de Tumor/metabolismo , Simulación del Acoplamiento Molecular , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Variaciones en el Número de Copia de ADN , Pronóstico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/metabolismo , Biomarcadores , Desarrollo de Medicamentos , Encéfalo/metabolismoRESUMEN
OBJECTIVE: To investigate the value of using MDM2 amplification probe and DDIT3 dual-color, break-apart rearrangement probe fluorescence in situ hybridization (FISH) technique in the diagnosis of liposarcoma. METHODS: In the study, 62 cases of liposarcoma diagnosed in Peking University First Hospital from January 2015 to December 2019 were analysed for clinicopathological information. Of these 62 cases of liposarcoma, all were analysed for MDM2 amplification and 48 cases were analysed for DDIT3 rearrangement using a FISH technique. Our study aimed to evaluate the status of MDM2 and DDIT3 by FISH in liposarcoma and correlate it with diagnosis of different subtypes of liposarcoma. The subtypes of liposarcoma were classified according to the FISH results, combined with the relevant clinicopathological features. RESULTS: The patients aged 31-89 years (mean: 59 years) with a 1.75:1 male to female ratio. Histologically, there were 20 cases of atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLPS), 26 cases of dedifferentiated liposarcoma (DDLPS), 13 myxoid liposarcoma (MLPS) and 3 pleomorphic liposarcoma (PLPS). Tumors with DDLPS (23/26) and WDLPS (8/20) were localized retroperitoneally, while both tumours of MLPS and PLPS were localized extra-retroperitoneally, and the difference of sites among the four subtypes of liposarcoma was statistically significant (P < 0.05). Histologically, varied mucoid matrix could be observed in the four subtypes of liposarcoma, and the difference was statistically significant (P < 0.05). MDM2 gene amplification was demonstrated in all cases of ALT/WDLPS and DDLPS (100%, 20/20 and 26/26 respectively); DDIT3 gene rearrangement was noted only in MLPS (100%, 13/13); most cases of DDLPS (96.2%, 25/26) and ALT/WDLPS (83.3%, 5/6, 6 cases selected for detection) demonstrated the picture of amplification of the DDIT3 telomeric tag. According to the instructions of DDIT3 break-apart rearrangement probe, the 5' telomere probe and 3' centromere probe spanned but did not cover the DDIT3 gene itself, on the contrary, the 5' telomere probe covered the CDK4 gene, while the DDIT3 and CDK4 gene were located adjacent to each other on chromosome, therefore, when the amplification signal appeared on the telomeric tag of the DDIT3 rearrangement probe, it indeed indicated the CDK4 gene amplification rather than the DDIT3 gene rearrangement. Then the 10 cases with DDIT3 telomeric tag amplification were selected for CDK4 and DDIT3 gene amplification probe FISH tests, and all the cases showed CDK4 gene amplification (100%, 10/10) and two of the 10 cases demonstrated co-amplification of CDK4 and DDIT3 (20%, 2/10); DDIT3 polysomy detected by DDIT3 gene rearrangement probe was found in 1 case of DDLPS and 2 cases of PLPS (66.7%, 2/3) with morphology of high-grade malignant tumour and poor prognosis. CONCLUSION: Our results indicate that a diagnosis of different subtype liposarcoma could be confirmed based on the application of MDM2 and DDIT3 FISH, combined with clinicopathological findings. It is also noteworthy that atypical signals should be correctly interpreted to guide correct treatment of liposarcomas.
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Lipoma , Liposarcoma , Masculino , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Quinasa 4 Dependiente de la Ciclina/análisis , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 4 Dependiente de la Ciclina/metabolismo , Liposarcoma/diagnóstico , Liposarcoma/genética , Liposarcoma/patología , Lipoma/diagnóstico , Lipoma/genética , Lipoma/patología , Amplificación de Genes , Factor de Transcripción CHOP/genética , Proteínas Proto-Oncogénicas c-mdm2/análisis , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismoRESUMEN
OBJECTIVE@#To investigate the value of using MDM2 amplification probe and DDIT3 dual-color, break-apart rearrangement probe fluorescence in situ hybridization (FISH) technique in the diagnosis of liposarcoma.@*METHODS@#In the study, 62 cases of liposarcoma diagnosed in Peking University First Hospital from January 2015 to December 2019 were analysed for clinicopathological information. Of these 62 cases of liposarcoma, all were analysed for MDM2 amplification and 48 cases were analysed for DDIT3 rearrangement using a FISH technique. Our study aimed to evaluate the status of MDM2 and DDIT3 by FISH in liposarcoma and correlate it with diagnosis of different subtypes of liposarcoma. The subtypes of liposarcoma were classified according to the FISH results, combined with the relevant clinicopathological features.@*RESULTS@#The patients aged 31-89 years (mean: 59 years) with a 1.75:1 male to female ratio. Histologically, there were 20 cases of atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLPS), 26 cases of dedifferentiated liposarcoma (DDLPS), 13 myxoid liposarcoma (MLPS) and 3 pleomorphic liposarcoma (PLPS). Tumors with DDLPS (23/26) and WDLPS (8/20) were localized retroperitoneally, while both tumours of MLPS and PLPS were localized extra-retroperitoneally, and the difference of sites among the four subtypes of liposarcoma was statistically significant (P < 0.05). Histologically, varied mucoid matrix could be observed in the four subtypes of liposarcoma, and the difference was statistically significant (P < 0.05). MDM2 gene amplification was demonstrated in all cases of ALT/WDLPS and DDLPS (100%, 20/20 and 26/26 respectively); DDIT3 gene rearrangement was noted only in MLPS (100%, 13/13); most cases of DDLPS (96.2%, 25/26) and ALT/WDLPS (83.3%, 5/6, 6 cases selected for detection) demonstrated the picture of amplification of the DDIT3 telomeric tag. According to the instructions of DDIT3 break-apart rearrangement probe, the 5' telomere probe and 3' centromere probe spanned but did not cover the DDIT3 gene itself, on the contrary, the 5' telomere probe covered the CDK4 gene, while the DDIT3 and CDK4 gene were located adjacent to each other on chromosome, therefore, when the amplification signal appeared on the telomeric tag of the DDIT3 rearrangement probe, it indeed indicated the CDK4 gene amplification rather than the DDIT3 gene rearrangement. Then the 10 cases with DDIT3 telomeric tag amplification were selected for CDK4 and DDIT3 gene amplification probe FISH tests, and all the cases showed CDK4 gene amplification (100%, 10/10) and two of the 10 cases demonstrated co-amplification of CDK4 and DDIT3 (20%, 2/10); DDIT3 polysomy detected by DDIT3 gene rearrangement probe was found in 1 case of DDLPS and 2 cases of PLPS (66.7%, 2/3) with morphology of high-grade malignant tumour and poor prognosis.@*CONCLUSION@#Our results indicate that a diagnosis of different subtype liposarcoma could be confirmed based on the application of MDM2 and DDIT3 FISH, combined with clinicopathological findings. It is also noteworthy that atypical signals should be correctly interpreted to guide correct treatment of liposarcomas.
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Masculino , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Quinasa 4 Dependiente de la Ciclina/metabolismo , Liposarcoma/patología , Lipoma/patología , Amplificación de Genes , Factor de Transcripción CHOP/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismoRESUMEN
Sarcomas are rare tumours that represent less than 1% of all malignant tumours in adults. Liposarcomas are among the most common malignant mesenchymal tumours. They are preferentially located in the limbs and the retroperitoneum. Liposarcomas primarily arising in the digestive tract are exceptional with a few cases reported in the literature. Their clinical presentation is variable and the symptoms are not specific. Anatomopathological examination remains the gold standard for the diagnosis and the classification of these tumours, which are divided into 5 histological types according to the 5th edition of the WHO classification of soft tissue tumours. We report two observations of unusual digestive liposarcomas, located in the oesophagus and the colon, emphasizing the variability of the diagnostic challenges, depending on the clinical presentation, the histological type and the analysed material.
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Liposarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Adulto , Tracto Gastrointestinal , Humanos , Liposarcoma/diagnósticoRESUMEN
Breast cancer is predominant causes of mortality in women worldwide. Genetic polymorphisms have a significant role in breast cancer aetiology. TP53 and its inhibitor the murine double minute 2 (MDM2) genes encode proteins that have crucial functions in the DNA damage response. The allelic variations within these genes could influence the susceptibility to breast cancer. MDM2 promotor polymorphism rs937283A/G has a role in susceptibility to cancer and modifies the promoter activity. In the present case-control study, the association of MDM2 rs937283A/G polymorphism and breast cancer susceptibility in Saudi women with samples of 137 breast cancer patients, and 98 healthy controls were explored. MDM2 gene polymorphism rs937283A/G was genotyped by polymerase chain reaction restriction fragment length polymorphism and confirmed by sequencing. The results revealed that rs937283A/G variant is significantly increases the risk of breast cancer in Saudi women (p-value = 0.0078). Moreover, rs937283A/G polymorphism was associated with high risk of breast cancer in estrogen positive breast cancer patients (p-value = 0.0088), progesterone positive breast cancer patients (p-value = 0.0043), human epidermal growth factor receptor 2 negative breast cancer patients (p-value = 0.0026), and triple negative breast cancer patients where (p-value = 0.0003). Positive association between increased breast cancer risk and rs937283 variant in premenopausal Saudi women, below 50 years of age, was demonstrated (p-value = 0.0023). Collectively, MDM2 rs937283A/G polymorphism could act as a possible biomarker for breast cancer susceptibility in Saudi women.
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OBJECTIVE: The current research was conducted to study the association between the SNP309 and del1518 polymorphisms with the breast cancer in the patients with the Kurdish ethnic background from western Iran. Also, a systematic review of the relevant case-control studies on the MDM2 polymorphisms in the patients with breast cancer was performed. METHODOLOGY: Two mL of peripheral blood was taken from 100 patients with breast cancer and 100 healthy individuals. The frequencies of MDM2 SNP309 and del1518 genotypes and alleles were determined using the PCR-RFLP and PCR methods, respectively. RESULTS: The frequency of the TT, TG, and GG of MDM2-SNP309 genotypes in the patients was obtained as 23%, 52%, and 25%, and they were equal to 22%, 40%, and 38% in the control group, respectively. Also, considering the MDM2-del1518 polymorphism, the frequencies of ins/ins, ins/del, and del/del genotypes were equal to 52%, 41%, and 7% in the breast cancer group and they were equal to 62, 30, and 8% in the control group, respectively. Analysis of the results indicated that the GG genotype plays a protective role for the breast cancer in the recessive model (GG vs TT + TG) of SNP309 (χ2 = 3.916, P = .048, and OR = 0.54). CONCLUSION: Our findings revealed that the GG genotype of MDM2-SNP309 can play a protective role in the breast cancer disease. Also, our systematic review indicated that the SNP309, SNP285, and del1518 of MDM2 gene in different populations mostly did not have a significant association with the risk of breast cancer.
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Neoplasias de la Mama , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Adulto , Anciano , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Humanos , Irán , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND/AIMS: Bangladesh is a densely populated country with an increased incidence of lung cancer, mostly due to smoking. Therefore, elucidating the association of mouse double minute 2 homolog (MDM2) single nucleotide polymorphism (SNP) 309 (rs2279744) with lung cancer risk from smoking in Bangladeshi population has become necessary. METHODS: DNA was extracted from blood samples of 126 lung cancer patient and 133 healthy controls. The MDM2 SNP309 was genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), using the restriction enzymes MspA1I. Logistic regression was then carried out to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of lung cancer. A meta-analysis of SNP309 was also carried out on 12,758 control subjects and 11,638 patient subjects. RESULTS: In multivariate logistic regression, significantly increased risk of lung cancer was observed for MDM2 SNP309 in the dominant model (TG + GG vs. TT: OR, 2.13; 95% CI, 1.29 to 3.53). Stratification analysis revealed that age, sex, obesity, and smoking also increases the risk of lung cancer when carrying the MDM2 SNP309. Our meta-analysis revealed that MDM2 SNP309 was considerably associated with lung cancer in Asian populations (TG + GG vs. TT: OR, 1.32; 95% CI , 1.12 to 1.56; p = 0.019 for heterogeneity). CONCLUSION: The MDM2 SNP309 was associated with high risk of lung cancer in Bangladeshi and Asian population, particularly with increased age, smoking, and body mass index.
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Neoplasias Pulmonares , Proteínas Proto-Oncogénicas c-mdm2 , Animales , Estudios de Casos y Controles , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Ratones , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-mdm2/genética , Factores de RiesgoRESUMEN
BACKGROUND: The aim of this study was to investigate the correlation between MDM2 T309G single nucleotide polymorphism (SNP) and esophageal cancer susceptibility through pooling the open published data. METHODS: By systematic searching the databases of Medline, EMBASE, CBM and CNKI, the case-control or cohort studies related to MDM2 T309G single nucleotide polymorphism and esophageal cancer risk were screened. Genetic phenotype data of T309G single nucleotide was extracted from the original included studies. The correlation between MDM2 T309G single nucleotide polymorphism and esophageal cancer susceptibility was demonstrated by the odds ratio (OR) and its corresponding 95% confidence interval (95% CI). Publication bias was investigated by Egger's line regression test and begg's funnel plot. RESULTS: After systematic searching of the relevant database, nine publications were finally included in the present study. The combined data demonstrated that the subjects with the G genotype had an increased risk of developing esophageal cancer in dominant (OR = 1.13, 95% CI: 1.00-1.27, P = 0.043), recessive (OR = 1.27, 95% CI: 1.12-1.45, P = 0.000) and homozygous (OR = 1.34, 95% CI:1.04-1.74, P = 0.024) genetic model through random or fixed data pooling method. Both begg's and Egger's line regression test indicated no significant publication bias. CONCLUSION: Based on the present data, there was a significant correlation between MDM2 T309G single nucleotide polymorphism and esophageal cancer susceptibility. Individuals with G genotype may have an increased risk of developing esophageal cancer.
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Biomarcadores de Tumor/genética , Neoplasias Esofágicas/patología , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-mdm2/genética , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/genética , Humanos , Pronóstico , Factores de RiesgoRESUMEN
The giant fibrovascular polyp of the esophagus is a rare, benign and typical entity described in 1957. This lesion is easily identifiable in its macroscopic and microscopic aspects. However, recent studies question the existence of the giant fibrovascular polyp of the esophagus. The demonstration of an amplification of the MDM2 gene poses the diagnosis of well-differentiated liposarcoma. We describe here a case of an esophagus polyp in a 67-year-old man. The diagnosis of giant fibrovascular polyp of the esophagus was initially retained. Secondly, the immunohistochemical and fluorescence in situ hybridization techniques showed amplification of the MDM2 gene and reclassified the lesion to a well-differentiated liposarcoma. The search for an undifferentiated contingent is essential to not ignore a dedifferentiated liposarcoma, which is a high-grade sarcoma with a poorer prognosis.
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Neoplasias Esofágicas/genética , Liposarcoma/genética , Pólipos/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Anciano , Diagnóstico Diferencial , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Amplificación de Genes , Humanos , Liposarcoma/diagnóstico , Liposarcoma/patología , Masculino , Pólipos/diagnóstico , Pólipos/patología , Tomografía Computarizada por Rayos XRESUMEN
Murine double minute clone 2 oncoprotein (MDM2) is a key component in the regulation of the tumour suppressor p53. The association between the MDM2 polymorphism and gastric cancer (GC) has been investigated in Turkish population. In the present case-control study, the aim was to investigate the association between genetic polymorphisms of the MDM2 gene (a major regulator of p53 function) and primary GC risk in a Turkish population. The polymorphism, T309G (rs2279744) in the MDM2 gene was determined in patients with GC (n=65) and in healthy control subjects (n=67) using the polymerase chain reaction-restriction fragment length polymorphism method. The findings were evaluated using logistic regression and χ2 tests. No statistically significant differences were observed between the control subjects and patients with GC regarding smoking status. A comparison between GC cases and control subjects indicated a statistically significant difference for family history of cancer [odds ratio (OR)=0.17; 95% confidence interval (CI), 0.05-0.56; χ2=0.19; P=0.01]. A significant difference was identified in the GG genotype distribution between GC patients and control subjects (OR=4.58; 95% CI, 1.18-17.79; P=0.022). Thus, the results of the present study indicate that the MDM2 gene T309G intron (GG) genotype may be an important risk factor for GC development in the Turkish population.
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The p53 gene and MDM2 gene play critical roles in cell cycle arrest and apoptosis together. Here, we evaluated the associations of prostate cancer risk and survival with the joint effects of mdm2 and p53 polymorphisms. Totally 1,193 cases and 1,310 age frequency-matched controls were included in the study. Prostate cancer patients were followed to determine the intervals of overall survival and disease-free survival. The Pro72Arg Pro allele (homozygous and heterozygous) were significantly associated with prostate cancer risk with an odds ratio (OR) of 0.77 [95% confidence interval(CI), 0.64-0.93]. SNP309 T alleles were associated with a significantly decreased prostate cancer risk among Pro72Arg Pro alleles carriers (OR=0.79, 95% CI, 0.64-0.98). In addition, compared with the Pro72Arg Pro alleles and SNP309 G homozygous, patients carrying both SNP309 T alleles and Pro72Arg Arg homozygous had more favorable disease-free survival (hazard ratio [HR] = 0.59, 95% CI, 0.38-0.93). Our results indicated that SNP309 and Pro72Arg polymorphisms may jointly contribute to the etiology and prognosis of prostate cancer.
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Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Heterocigoto , Homocigoto , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Fenotipo , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/terapia , Factores Protectores , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the association between potentially functional MDM2 oncogene, E3 ubiquitin protein ligase (MDM2) T309G polymorphism and susceptibility to oesophageal or gastric cancer. METHODS: Two investigators independently searched the PubMed and Chinese National Knowledge Infrastructure databases for studies published before September 2013. RESULTS: Pooled results showed that the variant homozygous 309 GG genotype (versus TT) was significantly associated with increased risk of both oesophageal (odds ratio [OR] 0.77; 95% confidence interval [CI] 0.65, 0.90) and gastric cancer (OR 0.52; 95% CI 0.38, 0.72). Subgroup analysis revealed a 309 GG-associated increased risk for both cancer types in Asian populations, particularly among Chinese and Japanese ethnicity. When stratified for Helicobacter pylori infection and histological type of gastric cancer, the 309 GG-related risk was higher in H. pylori-positive patients (T versus G: OR 0.37; 95% CI 0.22, 0.63) and the association was stronger with intestinal (TT + TG versus GG: OR 0.68; 95% CI 0.54, 0.87) rather than diffuse gastric-cancer type. CONCLUSIONS: The MDM2 T309G polymorphism may be significantly associated with increased susceptibility to oesophageal or gastric cancer, particularly among Eastern Asian populations.
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Neoplasias Esofágicas/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligasas/genética , Estudios de Casos y Controles , Humanos , Pronóstico , Factores de RiesgoRESUMEN
Objective:To define the expression levels of MDM2 gene in nasopharyngeal carcinoma (NPC)and its relationship with p53 protein expression and EB virus latent infection. Method :MDM2 gene expression atmRNA and protein levels,p53 protein and EB virus DNA were detected by nonradioactive in situ hybridization(ISH) ,immunohistochemistry(IHC) and polymerase chain reaction (PCR) separately in 46 cases of NPC tissuesand 12 cases of chronic inflammation of nasopharyngeal epithelium (CINE). Result: Fourteen cases of NPCshowed MDM2 mRNA and protein overexpression, 38 cases were p53 protein positive,and 43 cases were EBV-DNA positive. Neither MDM2 nor p53 protein was expressed in any case of CINE. MDM2 expression was signifi-cantly related to p53 protein expression ( P ＜0. 05), but not to EB virus latent infection in NPC. Conclusion:MDM2 gene may play an important role in the pathogenesis of NPC through interacting with p53 protein.
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Two new cases of leiomyosarcoma of the esophagus, one with an associated squamous cell carcinoma, are presented with review of literature. lmmunohistochemical study of MDM2 gene is performed upon these cases, and one case revealed overexpression of the MDM2 protein, whereas the other case showed negative result. And the pathological significance of MDM2 gene expression in esophageal leimyosarcoma is discussed, as, to our knowlege, no esophageal leiomyosarcoma with confirmed MDM2 gene amplification has been reported in the literature, to date. Gross character of these tumors was polypoid. Microscopically, the tumors consisted of interlacing fascicles of elongated spindle-shaped cells. Mitoses could be found without difficulty, with more than five per 10 high power fields. The tumor cells of the both cases showed imunohistochemical reactivity for vimentin and actin. Electron microscopically parallel arrays of myofilaments with interspersed dense bodies in spindle cell components were confirmed. The itera-literature regarding the association of leiomyosarcoma with epithelial malignancy in the gastrointestinal tract as well as esophagus is reviewed, and we found that this is a highly unusual occurrences(3 cases reported so far).