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1.
Using the technique of differential hybridization of a human fetal brain library, we have identified a novel gene, brain 3 (BR-3). This gene is not expressed in normal human brain tissue samples but is expressed at high levels in human low-grade glioma tissue samples. We have cloned and sequenced the full-length cDNA corresponding to this gene. Data base search analysis indicated that the BR-3 gene has strong homology to a genomic sequence present on chromosome 1 but no homology to expressed genes. Open reading frame analysis has indicated the presence of a 71 amino acids long protein sequence. A data base search for the protein sequence homology showed no similarity to known sequences. Expression analysis of BR-3 indicated that it is expressed at high level in six out of seven low-grade glioma samples analyzed. In addition low levels of BR-3 gene expression was observed in six out of seven anaplastic astrocytoma tissue samples analyzed. BR-3 expression was observed in four of eight glioblastoma samples analyzed. Expression analysis of normal human tissues indicated that it is expressed in kidney, skeletal muscle, lung, spleen and heart. No expression of the BR-3 gene was observed in brain, liver or testes tissue. To understand the role of the BR-3 gene in cancer in general, we studied its expression in other cancer cell lines. Except for lung and ovarian carcinoma, the BR-3 gene is expressed in breast carcinoma, colon adenocarcinoma, prostatic adenocarcinoma, and pancreatic adenocarcinoma tissue samples. On the basis of its sequence, unique expression pattern, we conclude that BR-3 gene product may play a critical role in the genesis of human gliomas tumors.  相似文献   

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The grading of dysplasia in Barrett's esophagus has prognostic importance, however observer variation limits the reliability of simple histological analysis alone. We investigated Ki-67, p53 and Bcl-2 expression in Barrett's esophagus, in the sequence from Barrett's low-grade dysplasia to high-grade dysplasia and infiltrating adenocarcinoma. Forty-four esophagectomy specimens were utilized: 39 specimens with esophageal dysplasia and adenocarcinoma and 5 specimens with esophageal dysplasia only. This gave 83 sections (2 sections for specimens with dyplasia and carcinoma) examined from 44 patients. The sections were examined for Ki-67, p53 and Bcl-2 reactivity by immunohistochemistry. Low-grade dysplasia was present in 14 sections, high-grade dysplasia in 30 sections and carcinoma in 39 sections. Ki-67 expression occurred in 2 out of 14 (14%) sections with low-grade dysplasia, in 22 out of 30 (73%) sections with high-grade dysplasia and in 34 out of 39 (87%) sections with carcinoma (p<0.001). p53 protein expression was found in 1 of 14 (7%) sections with low-grade dysplasia, in 18 of 30 (60%) sections with high-grade dysplasia and in 33 of 39 (85%) sections with carcinoma (p<0.001). Expression of Bcl-2 was found in 11 of 14 (84%) sections with low-grade dysplasia but immunoreactivity was not seen in any section with high-grade dysplasia or Barrett's carcinoma. Our results indicate that overexpression of Ki-67, Bcl-2 protein and p53 mutations can be identified as early events during neoplastic progression in Barrett's esophagus. These data support the hypothesis that, in the progression of Barrett's metaplasia to adenocarcinoma, the balance of proliferation/apoptosis plays an important role.  相似文献   

4.
It has been reported that there is an inverse correlation between the immunohistochemical expression of Rb2/p130, a member of the retinoblastoma gene family, and the degree of malignancy in at least some histological types. In order to investigate the expression of this protein in gliomas, we evaluated 58 samples from patients with resected gliomas. We focused on the relationship between the degree of malignancy of the glioma and the immunohistochemical detection of Rb2/p130. Expression of Rb2/p130 was observed in 38 glioma specimens (65.5%), including a high expression level in low-grade glioma specimens (>30% positive cells in 84% of tumors) and a low expression level in high-grade glioma specimens (>30% positive cells in 12% of tumors). The most aggressive of the gliomas exhibited very low to undetectable levels of Rb2/p130. Moreover, we observed an inverse correlation between Rb2/p130 expression and the degree of malignancy. These findings suggest that the differentiation of gliomas might be partially mediated by the Rb2/p130 gene, and that Rb2/p130 expression can additionally be an indicator of a better prognosis in patients with gliomas.  相似文献   

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MUC1 expression has been described as a predictor for tumor progression and worsening of prognosis in various human neoplasms. However, little is known about the role of MUC1 expression in pulmonary metastatic tumors. The aim of this study is to examine the clinicopathological significance of MUC1 expression in pulmonary metastatic tumors (PMT). One hundred forty-seven patients with PMT who underwent (18)F-FDG PET before metastasectomy were included in this study. Tumor sections were stained by immunohistochemistry for MUC1, glucose transporter 1 (Glut1), hypoxia-inducible-1α (HIF-1α) and vascular endothelial growth factor (VEGF). (18)F-FDG uptake and the expression of these biomarkers were correlated in primary lung cancer. MUC1 expression pattern was classified into high-grade polarized expression (HP), low-grade polarized expression (LP), or depolarized expression (DP) group. Of 147 patients, HP, LP and DP group were 9 (6%), 114 (78%) and 24 (16%), respectively. The expression of Glut1, HIF-1αand VEGF, and (18)F-FDG uptake were significantly higher in DP group than HP or LP groups. MUC1 expression with HP and DP pattern was significantly higher in primary lung cancer than in PMT, whereas, MUC1 expression with LP pattern yielded a significantly high positive rate in PMT. LP group was recognized in the majority of patients with pulmonary metastatic adenocarcinoma, especially colon cancer, whereas, HP group was significantly low in pulmonary metastatic adenocarcinoma as compared with primary adenocarcinoma. Polarized MUC1 has a different expression pattern between primary and metastatic tumors with adenocarcinoma, and depolarized MUC1 is closely associated with glucose metabolism and hypoxia.  相似文献   

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To analyze the clinical characteristics and prognostic factors in patients with glioma in an academic institute in China. From October 2004 to August 2010, total 1,285 patients were diagnosed as glioma at the Glioma Center of Beijing Tiantan Hospital. Clinical and molecular pathology features and survival rates were analyzed. The median overall survival (OS) times were 78.1, 37.6 and 14.4 months for low-grade glioma (WHO grade II), anaplastic glioma (WHO grade III) and glioblastoma (WHO grade IV), respectively. In patients with low-grade glioma, age, preoperative Karnofsky performance scale (KPS), pathological type, radiotherapy, O6-methylguanine-DNA methyltransferase (MGMT) expression and Ki-67 expression, were significantly associated with OS in multivariate analyses; and preoperative KPS and radiotherapy were significantly associated with progression-free survival (PFS). For anaplastic gliomas, age, preoperative KPS, pathological type, extent of resection, radiotherapy, p53 expression and phosphatase and tensin homolog (PTEN) expression were associated with OS. For glioblastomas, age, preoperative KPS, pathology type, extent of resection, radiotherapy and chemotherapy were associated with OS; and age, gender, preoperative KPS, extent of resection, radiotherapy and chemotherapy were associated with PFS. This is the largest survey for glioma management in China to date. We found significant differences in age, presenting symptoms and the expression of p53, MGMT, PTEN, and Ki-67 among patients with different types of glioma. Age, preoperative KPS, tumor grades, radiotherapy, chemotherapy and Ki-67 expression were significantly associated with clinical prognosis.  相似文献   

8.
目的探讨结直肠上皮内瘤变的临床病理特征。方法回顾性分析18例结直肠上皮内瘤变患者的临床资料,其中低级别上皮内瘤变2例,高级别上皮内瘤变16例。行肠镜下电切术7例,经肛门局部切除术2例,肠段切除术2例,根治性手术5例,全结肠切除术1例,剖腹探查术1例。结果 18例中术前诊断为低级别上皮内瘤变2例,术后病理结果为腺瘤伴低级别上皮内瘤变;高级别上皮内瘤变16例,术后病理结果为腺癌8例,高级别上皮内瘤变8例。高级别上皮内瘤变患者中50%病理结果为腺癌。结论术前高度怀疑高级别上皮内瘤变实为腺癌,如果不涉及保肛问题,宜首选病变肠段切除,如术前或术中可确诊为腺癌,则应行根治性切除手术。  相似文献   

9.
We report the prognostic significance of tumor CT contrast enhancement within histological subgroups in 831 consecutive adult glioma patients of high-grade (n=516) and low-grade (n=315) histology. In the present report, a negative prognostic factor is associated with shortened survival. Methods: Survival analysis including Kaplan-Meier plots, log-rank tests, Cox analysis, and Aalen's linear model as implemented in SPSS and S-PLUS. Results: Sensitivity and specificity of contrast enhancement as a test for high-grade glioma was 0.87 and 0.79, respectively. Enhancement was a strong negative prognostic factor comparable to high-grade histology in the total patient population. Enhancement was also a negative prognostic factor within the subgroups adult high-grade (Grade 3–4), anaplastic (Grade 3), and low-grade (Grade 1–2) gliomas (p < 0.001). The prognostic implications of initial enhancement declined in high-grade patients surviving beyond 36 months. Tumor contrast enhancement or calcifications (in parentheses) were present in 96% (3.6%) of glioblastomas, in 87% (7.4%) of high-grade gliomas, in 56.5% of anaplastic gliomas, and in 21% (16.2%) of low-grade gliomas. Calcification was a positive prognostic factor within the high-grade group of patients (p < 0.0001). Conclusion: Enhancement was a major prognostic factor comparable to high-grade histology in this glioma patient population. Enhancement was a negative prognostic factor within each of the adult subgroups high-grade, anaplastic (grade 3), and low-grade gliomas. Enhancement was strongly associated with but not pathognomonic for high-grade histology.  相似文献   

10.
AIM: To explore useful prognostic factors for mucinous adenocarcinoma (MAC) in the colon and rectum.METHODS: MAC was divided into low- and high-grade types based on the degree of structural differentiation; low-grade MAC arisen from well to moderately differentiated adenocarcinoma and papillary carcinoma, and high-grade MAC from poorly differentiated adenocarcinoma and signet ring cell carcinoma. Immunohistochemically, the expression of 2 types of MUC1 (MUC1/DF and MUC1/CORE), MUC2, 2 types of MUC5AC (MUC5AC/CHL2 and HGM), MUC6, CDX2, and CD10 was examined in 16 cases of MAC consisting of 6 low- and 10 high-grade types.RESULTS: MUC1/DF3 was expressed in 3 of 6 low-grade MAC (50%) and 10 of 10 high-grade MAC (100%). MUC1/CORE was expressed in 1 of 6 low-grade MAC (16.7%) and 7 of 10 high-grade MAC (70%). MUC2 was expressed in all MAC regardless of the grade. MUC5AC was expressed in 6 of 6 low-grade MAC (100%) and 4 of 10 high-grade MAC (40%). HGM was expressed in 5 of 6 low-grade MAC (83.3%) and 6 of 10 high-grade MAC (60%). Expression of MUC6 and CD10 was undetected in all MAC regardless of the grade. CDX2 was expressed in 5 of 6 low-grade MAC (83.3%) and 7 of 10 high-grade MAC (70%). Taken together, MUC1/DF3 was expressed significantly more frequently in high-grade MAC than in low-grade, and MUC5AC/CHL2 was expressed significantly more frequently in low-grade MAC than in high-grade.CONCLUSION: It is proposed that MUC1/DF3 and MUC5AC/CHL2 immunostaining is useful to discriminate high-grade MAC from low-grade MAC.  相似文献   

11.
Tumor grade and molecular variants influence the survival of patients with glioma. The apparent diffusion coefficient (ADC) map is a non-invasive tool for evaluating the outcomes and response to therapy in glioma. In this study, we investigated the correlation between the tumor grade and prognostic biomarkers with the ADC in glioma patients. Eighty-two patients with supratentorial glioma were identified via analysis of surgical specimens and neuroradiological data. Using the World Health Organization grade, histological subtype, and molecular variants (1p/19q codeletion, isocitrate dehydrogenase 1/2 mutation, Ki-67 index, O6-methylguanine DNA methyltransferase, P53, and vascular endothelial growth factor immunoactivity) as prognostic biomarkers, we performed receiver operating characteristic analysis and multiple linear regression to assess the association between the magnetic resonance diffusion parameter and mean ADC and the prognostic factors of glioma pathology. Univariate analysis and multiple linear regression revealed inverse correlations between the ADC values and the tumor grade, oligodendrocytoma histology, and 1p/19q codeletion. A threshold mean ADC value could predict the 1p/19q chromosomal status in WHO II gliomas with 72 % sensitivity and 88 % specificity (area under the curve 0.82, 95 % confidence interval 0.68–0.97) and could distinguish low-grade glioma with low-risk factors from the high-risk group (P < 0.01). The mean ADC value could be used as a non-invasive tool to evaluate the prognosis of supratentorial glioma patients. A threshold mean ADC value could be used to predict the 1p/19q codeletion and to identify low-risk low-grade gliomas (LGGs). Lower ADC values are indicative of a favorable prognosis in LGGs.  相似文献   

12.
Combined deletion of chromosomes 1p and 19q is associated with improved prognosis and responsiveness to therapy in patients with anaplastic oligodendroglioma. The deletions usually involve whole chromosome arms, suggesting a t(1;19)(q10;p10). Using stem cell medium, we cultured a few tumors. Paraffin-embedded tissue was obtained from 21 Mayo Clinic patients and 98 patients enrolled in 2 North Central Cancer Treatment Group (NCCTG) low-grade glioma trials. Interphase fusion of CEP1 and 19p12 probes detected the t(1;19). 1p/19q deletions were evaluated by fluorescence in situ hybridization. Upon culture, one oligodendroglioma contained an unbalanced 45,XX,t(1;19)(q10;p10). CEP1/19p12 fusion was observed in all metaphases and 74% of interphase nuclei. Among Mayo Clinic oligodendrogliomas, the prevalence of fusion was 81%. Among NCCTG patients, CEP1/19p12 fusion prevalence was 55%, 47%, and 0% among the oligodendrogliomas, mixed oligoastrocytomas, and astrocytomas, respectively. Ninety-one percent of NCCTG gliomas with 1p/19q deletion and 12% without 1p/19q deletion had CEP1/19p12 fusion (P < 0.001, chi(2) test). The median overall survival (OS) for all patients was 8.1 years without fusion and 11.9 years with fusion (P = 0.003). The median OS for patients with low-grade oligodendroglioma was 9.1 years without fusion and 13.0 years with fusion (P = 0.01). Similar significant median OS differences were observed for patients with combined 1p/19q deletions. The absence of alterations was associated with a significantly shorter OS for patients who received higher doses of radiotherapy. Our results strongly suggest that a t(1;19)(q10;p10) mediates the combined 1p/19q deletion in human gliomas. Like combined 1p/19q deletion, the 1;19 translocation is associated with superior OS and progression-free survival in low-grade glioma patients.  相似文献   

13.
Methylation in the promoter region is one of the mechanisms through which tumor suppressors are inactivated, resulting in tumorigenesis and/or tumor progression. Herein, we studied the methylation status in the promoter region of the p14ARF tumor suppressor gene in 33 brain tissues isolated from glioma patients (astrocytomas) and compared to 12 brain tissues isolated from autopsy donors using methylation-specific polymerase chain reaction (MSP). The correlation between the expression of P14 and P53 was investigated using immunohistochemistry (IHC). The average percentage of methylation in the promoter region of p14ARF gene in brain samples from glioma patients is 39.4%, while 0 from autopsy donors. No difference in the methylation level between low-grade and high-grade gliomas was detected. The methylation status has no correlation with the prognosis in glioma patients. A significant correlation between the expression of mutant form of TP53 and the grade of the glioma was established. Furthermore, there was a negative correlation between methylation of the p14ARF promoter and the expression of the mutant form of TP53. Therefore, our data suggest that methylation in the promoter region of the p14ARF gene may be used as a biomarker for the diagnosis of gliomas.  相似文献   

14.
目的 分析O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因启动子甲基化状态及其与胶质瘤临床病理特征、预后的关系。方法 收集2012年1月至2013年6月间行手术治疗的70例胶质瘤组织和14例非肿瘤患者正常脑组织,采用甲基化特异性 PCR法(MSP)检测MGMT甲基化水平,分析其与胶质瘤临床病理特征的关系。比较不同MGMT甲基化状态的高、低级别胶质瘤患者的总生存(OS),Cox比例风险回归模型分析影响低级别胶质瘤患者的OS的因素。结果 70例胶质瘤患者中48例(68.6%)MGMT基因启动子甲基化,而正常脑组织标本中仅2例(14.3%)MGMT甲基化,差异有统计学意义(P<0.05)。MGMT甲基化与年龄、性别、肿瘤类型、KPS评分、p53和Ki-67表达无关(P>0.05);与病理分级有关(P<0.05)。低级别脑胶质瘤患者中,MGMT甲基化患者中位OS为30个月,明显长于非甲基化者的11个月,差异具有统计学意义(P<0.05)。单因素分析显示WHO病理分级、烷化剂化疗、MGMT甲基化与低级别脑胶质瘤患者OS有关(P<0.05)。多因素分析WHOⅡ级、未接受烷化剂化疗、MGMT非甲基化是影响低级别胶质瘤患者OS的独立危险因素(P<0.05)。结论 MGMT甲基化与胶质瘤的发生、发展有关,在判断胶质瘤恶性度、评估预后及指导临床治疗方面具有一定的价值。  相似文献   

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目的:探讨结肠癌组织中E-cadherin的表达情况及其与结肠癌患者预后的相关性。方法:收集 2008年3月至2014年10月期间,我院普通外科接受手术治疗的大肠癌患者307例,采用免疫组织化学的方法检测肿瘤组织中E-cadherin的表达情况,统计学分析E-cadherin的表达情况与患者生存的关系。结果:E-cadherin主要表达于细胞膜上,在结肠癌组织中阳性表达率为36.8%,在正常组织中阳性表达率为100.0%,E-cadherin在癌组织中的阳性表达率明显低于正常组织。在高分化大肠癌组织中的阳性表达率为59.5%,在中分化组织中的阳性表达率为39.9%,在低分化组织中的阳性表达率为20.7%。有淋巴结转移的结肠癌组织中E-cadherin阳性表达率为23.3%,未发生淋巴结转移的组织中E-cadherin阳性表达率为45.5%。在Ⅲ期和Ⅳ期结肠癌患者中,E-cadherin阳性结肠癌患者生存时间明显比阴性患者长。多因素Cox回归分析提示,Ⅲ期和Ⅳ期结肠癌患者中E-cadherin表达情况、临床分期是结直肠癌患者OS独立的预后影响因素。结论:结肠癌组织中E-cadherin的表达情况是Ⅲ期和Ⅳ期结肠癌患者重要预后因素。  相似文献   

16.
MT1-MMP及MMP2在人脑胶质瘤中的表达及意义   总被引:3,自引:0,他引:3  
目的探讨膜型基质金属蛋白酶-1在人脑胶质瘤中的表达及其与肿瘤生物学行为和预后的关系。方法用免疫组织化学S-P法检测48例人脑胶质瘤组织和10例正常人脑组织中MT1-MMP和MMP2的表达。结果高级别胶质瘤组织(Ⅲ~Ⅳ)中MT1-MMP和MMP2的阳性表达率显著高于低级别胶质瘤组织(Ⅰ~Ⅱ),且两者的表达呈显著正相关性。在单因素生存分析中,MT1-MMP的表达与患者预后不良有关。结论MT1-MMP在恶性胶质瘤组织中高表达,与胶质瘤的进展和侵袭密切相关,可作为胶质瘤恶性表型的有用指标;MT1-MMP的阳性表达与患者的预后不良有关。MT1-MMP可能与MMP2的活化密切相关,直接或间接的促进脑胶质瘤的侵袭。  相似文献   

17.
Little is known about the expression of mitogens and other tumour-related substances in the cerebrospinal fluid (CSF) of glioma patients. The aim of the current study was to determine the presence of aberrant proteins in the CSF of patients with low-grade gliomas. Lumbar puncture was performed in 8 adult patients with supratentorial low-grade gliomas at the time of diagnosis and in 7 controls. Two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionisation time of flight mass spectrometry were used to detect and quantify deviant proteins in the CSF. Two isoforms of alpha(2)-Heremans-Schmid glycoprotein (AHSG) were identified and demonstrated in higher levels in patients with low-grade gliomas compared with the control group consisting of patients with mixed neurological diagnoses (p = 0.001 and p = 0.04, respectively). In 1 patient, the level of AHSG was significantly reduced after gross total resection of the tumour. AHSG appears in the present proteome screening as a novel substance in glioma research. This glycoprotein is expressed in the fetal human brain and is believed to be involved in the embryonic development of the neocortex. Further analyses are planned to determine the significance of the increased levels of AHSG in the CSF of patients with low-grade gliomas.  相似文献   

18.
王志勇  王萍 《现代肿瘤医学》2021,(16):2858-2862
目的:检测miR-134-5p在结肠腺癌组织中的表达,分析其临床意义。方法:选取2016年01月-2016年06月我院收治的84例结肠腺癌患者,选择肿瘤组织作为观察组,选择距肿物边缘>5 cm的正常结肠黏膜组织作为对照组,应用实时荧光定量PCR法检测两组组织中miR-134-5p的表达,应用免疫组化方法检测观察组中Ki67和BAX的表达。结果:观察组中miR-134-5p的表达明显低于对照组(P<0.05),观察组中miR-134-5p的表达在有无癌栓、不同浸润深度、有无淋巴结转移及不同TNM分期的表达中差异有统计学意义(P<0.05)。miR-134-5p的表达与增殖指数呈负相关性(P<0.05),miR-134-5p的表达与BAX的表达呈正相关性(P<0.05)。生存分析显示miR-134-5p的表达与生存时间相关(P<0.05)。结论:结肠腺癌中miR-134-5p低表达是结肠腺癌形成的重要分子因素,与临床生物学行为的进展有关,miR-134-5p的作用与对细胞增殖和凋亡的调节有关,miR-134-5p的表达可能与预后有关。  相似文献   

19.
张训  杨宏  谢清  陈盛强 《肿瘤学杂志》2011,17(2):118-121
[目的]探讨人脑胶质瘤组织中EphA2和MMP2的表达水平及相关性。[方法]采用免疫组织化学SP法检测69例胶质瘤组织、10例正常脑组织中EphA2和MMP2蛋白表达情况,分析两者表达水平与胶质瘤临床病理分级之间的关系及两者的相关性。[结果]正常脑组织、低级别胶质瘤组织(Ⅰ~Ⅱ级)和高级别胶质瘤组织(Ⅲ~Ⅳ级)中EphA2蛋白表达的阳性率分别为10.0%(1/10)、37.0%(10/27)、90.5%(38/42),差异有统计学意义(χ2=33.0826,P=0.000);正常脑组织、低级别胶质瘤组织和高级别胶质瘤组织中MMP2蛋白表达的阳性率分别为0、14.8%(4/27)、69.0%(29/42),差异有统计学意义(χ2=28.0869,P=0.000)。在胶质瘤组织中,EphA2与MMP2蛋白表达呈正相关(r=0.660,P=0.000)。[结论]EphA2与MMP2同时高表达于胶质瘤组织中,EphA2可能通过影响MMP2而促进肿瘤的侵袭与转移。  相似文献   

20.
BACKGROUND: Some patients with low-grade glioma have extraordinarily long survival times; current, early treatment does not prolong their lives. For this reason, therapies that sometimes have neurologic side effects are often deferred intentionally. METHODS: In a study of oligodendrogliomas, we used a quantitative method of MR analysis based on the S-transform to investigate whether codeletion of chromosomes 1p and 19q, a marker of good prognosis, could be predicted accurately by measuring image texture. RESULTS: Differences in texture were seen between tumors with codeletion of chromosomes 1p and 19q and those with intact 1p and 19q alleles on contrast-enhanced T1-weighted and T2-weighted MR images. Quantitative MR texture on T2 images predicted codeletion of chromosomes 1p and 19q with high sensitivity and specificity. CONCLUSIONS: This new method of MR image interpretation may have the potential to augment the diagnostic assessment of patients with suspected low-grade glioma.  相似文献   

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