Morphology and biology of cerebellar neuroblastomas

Summary A nodular neuroblastoma was partially removed from the cerebellar vermis of a 15-month-old boy. Postoperative irradiation and chemotherapy were performed. More than 5 years later, re-operation revealed a mature ganglioglioma. Problems relating to the maturation of ganglionic tumors are discussed. The present case emphasizes that it is not justified to regard all neuroblastomas of the central nervous system as highly malignant neoplasms (grade IV).     

Expression of TrkA,TrkB and TrkC in human neuroblastomas

There is considerable interest in the role of the TRK family of neurotrophin receptors in regulating the survival, growth and differentiation of normal and neoplastic nerve cells. Indeed, there is increasing evidence that TRK genes play an important role in the biology and clinical behavior of neuroblastomas, tumors of the peripheral nervous system. Evidence from several independent studies suggests that high expression of TrkA is an indicator of favorable outcome, and there is an inverse correlation between TrkA expression and N-myc amplification. In addition, some primary neuroblastomas differentiate in vitro in the presence of NGF but die in its absence. We have evidence that coexpression of full-length TrkB and BDNF is associated with N-myc amplification and may represent an autocrine survival pathway. Conversely, truncated TrkB is expressed predominantly in differentiated tumors. Finally, TrkC is expressed in favorable neuroblastomas, essentially all of which also express TrkA. In summary, the study of neurotrophin receptor expression and function in neuroblastomas may provide important insights into the role that these pathways play in the pathogenesis and clinical behavior of this tumor. Ultimately, these pathways may provide attractive targets for the development of therapy aimed at inducing differentiation or programmed cell death in these tumors.     

青年女性乳腺癌病理学特点及预后因素分析

目的 乳腺癌已是青年女性最常见的恶性肿瘤之一,青年乳腺癌患者也越来越受关注.本研究探讨青年女性乳腺癌(≤35岁)的临床病理学特点,分析影响患者临床预后的因素.方法 回顾性分析广西医科大学附属肿瘤医院2006-01-01-2011-01-01收治的127例≤35岁女性乳腺癌的临床资料,采用Kaplan-Meier法计算无疾病进展生存率和总生存率,Log-rank检验比较生存差异,Cox比例风险回归模型进行预后多因素分析.结果 全组病例TNM病理分期:Tis(原位癌)2例,Ⅰ期38例,Ⅱ期50例,Ⅲ期31例,Ⅳ期6例.5年总生存率、10年累积生存率Ⅰ期分别为97.4％(37/38)和94.7％(36/38),Ⅱ期为92.0％(46/50)和90.0％(45/50),Ⅲ期为71.0％(22/31)和71.0％(22/31),Ⅳ期为33.3％(2/6)和33.3％(2/6).5年无疾病进展生存率、10年累积无疾病进展生存率I期分别为89.5％(34/38)和89.5％(34/38),Ⅱ期为82.0％(41/50)和76.0％(38/50),Ⅲ期为54.8％(17/31)和51.6％(16/31),Ⅳ期为16.7％(1/6)和16.7％(1/6).Cox多因素回归分析显示,TNM分期(P＜0.01)和流产史(P[0.04)是影响5年总生存(overall survival,OS)的主要因素,TNM分期(P＜0.01)和身体质量指数(P=0.02)是影响10年累积OS的主要因素;TNM分期(P＜0.01)和术后放疗(P=0.02)是影响5年无疾病进展生存(progression free survival,PFS)的主要因素,TNM分期(P＜0.01)、流产史(P=0.01)和术后放疗(P＜0.01)是影响10年累积PFS的主要因素.结论 青年乳腺癌有着独特的临床病理学特点,TNM病理分期、术后放疗、肥胖和流产史是影响其预后的重要因素,早发现、早诊断及早治疗是良好预后的关键.     

儿童神经母细胞瘤36例临床特点及预后因素分析

目的:分析儿童神经母细胞瘤的临床特点、疗效及预后。方法:回顾分析2010年1月至2016年6月我院血液肿瘤科收治的36例神经母细胞瘤患儿的临床资料,采用Kaplan-Meier法进行生存分析。结果:36例患儿男20例,女16例,平均年龄25个月（5~47个月）。随访至2017年6月30日,中位随访时间:21.5个月（5~81个月）,2年总生存率（OS）61.9%,II期、III期、IV期分别为100%、65%、11.1%。结论:尽早明确神经母细胞瘤分期,给予合适的综合治疗方案,能明显减少化疗毒副反应、延长生存率,提高临床治愈率。     

High CCND1 amplification identifies a group of poor prognosis women with estrogen receptor positive breast cancer

CCND1 encodes for the cyclin D1 protein involved in G1/S cell cycle transition. In breast cancer the mechanism of CCND1 amplification, relationship between cyclin D1 protein expression and the key clinical markers estrogen receptor (ER) and HER2 requires elucidation. Tissue microarrays of primary invasive breast cancer from 93 women were evaluated for CCND1 amplification by fluorescent in‐situ hybridization and cyclin D1 protein overexpression by immunohistochemistry. CCND1 amplification was identified in 27/93 (30%) cancers and 59/93 (63%) cancers had overexpression of cyclin D1. CCND1 amplification was significantly associated with cyclin D1 protein overexpression (p < 0.001; Fisher's exact test) and both CCND1 amplification and cyclin D1 protein expression with oestrogen receptor (ER) expression (p = 0.003 and p < 0.001; Fishers exact test). Neither CCND1 amplification nor cyclinD1 expression was associated with tumor size, pathological node status or HER2 amplification, but high CCND1 amplification (Copy Number Gain (CNG) ≥ 8) was associated with high tumor grade (p = 0.005; chi square 7.915, 2 df) and worse prognosis by Nottingham Prognostic Index (p = 0.001; 2 sample t‐test). High CCND1 amplification (CNG ≥ 8) may identify a subset of patients with poor prognosis ER‐positive breast cancers who should be considered for additional therapy.     

肾细胞癌NDRG-1和E-cadherin表达及其与临床病理因素、MVD及预后的关系

目的:研究N-myc下游调节基因(NDRG-1)和上皮型钙粘素(E-cadherin)在肾细胞癌组织中的表达,探讨其与肾细胞癌临床病理因素、微血管密度(MVD)及预后的关系。方法:应用免疫组织化学SP法检测49例肾细胞癌组织及相对应的癌旁肾脏组织中NDRG-1、E-cadherin表达情况。结果:NDRG-1和E-cadherin在正常肾组织表达均高于肾细胞癌组织,差异有显著性(P<0.01);二者随肾细胞癌肿瘤组织学分级、临床分期增高表达减弱,有肾门淋巴结转移者表达低于无淋巴结转移者,E-cadherin表达降低还与肾盂浸润、肾静脉癌栓相关,差异均有显著性(P<0.05);NDRG-1和E-cadherin表达均与肾细胞癌MVD呈负相关性(P<0.05);NDRG-1和E-cadherin表达阴性病例术后存活时间均显著短于阳性病例(P=0.001);肾细胞癌组织中NDRG-1和E-cadherin表达无相关性(r=-0.253,P=0.086)。结论:NDRG-1和E-cadherin表达降低与肾细胞癌的浸润、转移及血管生成和生存时间密切相关,检测NDRG-1和E-cadherin可作为预测肾细胞癌浸润转移及预后有意义的指标。     

Aurora-A基因在神经母细胞瘤中的表达及其与临床分期、预后的关系

目的：检测Aurora-A基因在NB中的表达情况,并探讨其与临床分期及预后的关系,旨在发现新型、独立有效的预后标记物。方法：本院2005年-2009年20例NB冻存组织和2007年-2010年15例伴有骨髓转移的NB骨髓标本。另取10例节细胞神经瘤冻存组织作对照。采用实时荧光定量PCRSYBR Green I方法检测上述标本中Aurora-A基因mRNA的表达情况;采用SPSS 13.0软件进行统计学分析。结果：Aurora-A基因在10例节细胞神经瘤对照组中无表达,在35例NB标本中存在不同程度的表达,两组具有显著差异（P〈0.01）;Aurora-A基因在低分期组中低表达（0.225±0.096）,高分期组中高表达（0.659±0.079）（P〈0.01）;Aurora-A基因表达水平的高低与年龄有关,小于1岁者表达低（0.392±0.163）,大于等于1岁者表达高（0.578±0.237）（P〈0.05）;Aurora-A基因表达水平的高低与生存时间呈负相关（P〈0.01）。结论：Aurora-A基因在恶性NB中高表达,可能参与NB的恶性增殖;Aurora-A基因高表达患儿预后不良,可作为NB分子生物学预后标记物。     

肾细胞癌NDRG-1和E-cadherin表达及其与临床病理因素、MVD及预后的关系

目的：研究N-myc下游调节基因（NDRG-1）和上皮型钙粘素（E-cadherin）在肾细胞癌组织中的表达,探讨其与肾细胞癌临床病理因素、微血管密度（MVD）及预后的关系。方法：应用免疫组织化学SP法检测49例肾细胞癌组织及相对应的癌旁肾脏组织中NDRG-1、E-cadherin表达情况。结果：NDRG-1和E-cadherin在正常肾组织表达均高于肾细胞癌组织,差异有显著性（P〈0.01）;二者随肾细胞癌肿瘤组织学分级、临床分期增高表达减弱,有肾门淋巴结转移者表达低于无淋巴结转移者,E-cadherin表达降低还与肾盂浸润、肾静脉癌栓相关,差异均有显著性（P〈0.05）;NDRG-1和E-cadherin表达均与肾细胞癌MVD呈负相关性（P〈0.05）;NDRG-1和E-cadherin表达阴性病例术后存活时间均显著短于阳性病例（P=0.001）;肾细胞癌组织中NDRG-1和E-cadherin表达无相关性（r=-0.253,P=0.086）。结论：NDRG-1和E-cadherin表达降低与肾细胞癌的浸润、转移及血管生成和生存时间密切相关,检测NDRG-1和E-cadherin可作为预测肾细胞癌浸润转移及预后有意义的指标。     

Aurora-A基因在神经母细胞瘤中的表达及其与临床分期、预后的关系

目的:检测Aurora-A基因在NB中的表达情况,并探讨其与临床分期及预后的关系,旨在发现新型、独立有效的预后标记物。方法:本院2005年-2009年20例NB冻存组织和2007年-2010年15例伴有骨髓转移的NB骨髓标本。另取10例节细胞神经瘤冻存组织作对照。采用实时荧光定量PCRSYBR Green I方法检测上述标本中Aurora-A基因mRNA的表达情况;采用SPSS 13.0软件进行统计学分析。结果:Aurora-A基因在10例节细胞神经瘤对照组中无表达,在35例NB标本中存在不同程度的表达,两组具有显著差异(P<0.01);Aurora-A基因在低分期组中低表达(0.225±0.096),高分期组中高表达(0.659±0.079)(P<0.01);Aurora-A基因表达水平的高低与年龄有关,小于1岁者表达低(0.392±0.163),大于等于1岁者表达高(0.578±0.237)(P<0.05);Aurora-A基因表达水平的高低与生存时间呈负相关(P<0.01)。结论:Aurora-A基因在恶性NB中高表达,可能参与NB的恶性增殖;Aurora-A基因高表达患儿预后不良,可作为NB分子生物学预后标记物。     

人肺鳞癌组织中Caveolin-1的表达及预后意义

  目的   研究Caveolin-1在人肺鳞癌中的表达, 探讨Caveolin-1的表达与人肺鳞癌临床病理特征以及预后的关系。   方法   运用免疫组织化学法检测人肺鳞癌组织中Caveolin-1、PCNA的表达, 并结合患者的临床病理特征和生存情况进行分析。   结果   Caveolin-1在人肺鳞癌中阳性率显著低于正常肺组织(P < 0.001);Caveolin-1的表达与肺鳞癌的TNM分期(P=0.018) 及淋巴结状态(P=0.006) 有关。在人肺鳞癌组织中Caveolin-1与PCNA表达呈正相关(r=0.360, P=0.018)。生存分析显示肺鳞癌中Caveolin-1阳性组的生存时间显著低于阴性组(P=0.007), 在24例淋巴结未转移组中Caveolin-1阳性组的生存时间显著低于阴性组(P=0.002)。多因素Cox分析显示Caveolin-1阳性表达、高临床分期、支气管残端有癌残留的肺鳞癌患者术后生存时间较短。   结论   Caveolin-1的表达与肺鳞癌的恶性演进呈正相关; 其可促进肺癌细胞的增殖。Caveolin-1可作为评估肺鳞癌患者的不良预后指标。      

Treatment of children over the age of one year with unresectable localised neuroblastoma without MYCN amplification: Results of the SIOPEN study

BackgroundIn children older than 1 year with localised unresectable neuroblastoma (NB), treatment strategies are heterogeneous according to the national groups. The objective of this phase III non-randomised study was to evaluate the efficacy of conventional chemotherapy followed by surgery.Patients and methodsIn the presence of surgical risk factors (SRF), six courses of chemotherapy alternating Carboplatin–Etoposide and Vincristin–Cyclophosphamide–Doxorubicin were given, and surgical resection was attempted after four. Survival analyses were performed using an intention-to-treat approach. The main objective was to achieve a 5-year survival over 80%.ResultsOut of 191 registered children, 160 were evaluable. There were 62.5% older than 18 months and 52.5% had unfavourable histology according to International Neuroblastoma Pathology Classification (INPC). Chemotherapy reduced the number of SRFs by one third. Delayed surgery was attempted in 86.3% of patients and was complete or nearly complete in 74%. The 5-year EFS and OS were 76.4% and 87.6% respectively, with significant better results for patients younger than 18 months or with favourable histology.ConclusionThis strategy provides encouraging results in children older than 1 year or 12 months with localised unresectable NB without MYCN amplification. However, in children older than 18 months and with unfavourable histology, additional treatment is recommended.     

Impact of prospero homeobox-1 on tumor cell behavior and prognosis in colorectal cancer

Prospero homeobox 1 (PROX1) is up-regulated in colorectal cancer and plays an oncogenic role. In the present study, we sought to investigate the impact of PROX1 on oncogenic processes and to assess the prognostic value of PROX1 expression in colorectal cancer. A small interfering RNA or pcDNA6-myc vector was used to control PROX1 gene expression in colorectal cancer DLD1 and SW480 cell lines. The expression of PROX1 in colorectal cancer tissues was investigated by immunohistochemistry. Angiogenesis, lymphangiogenesis, and tumor cell proliferation were assessed by analyzing the expression of respective markers of these phenomena, CD34, D2-40, and Ki-67 after immunohistochemical staining. PROX1 knockdown decreased both umbilical vein endothelial cell invasion and tube formation, down-regulated the expression of VEGF-A and HIF-1α, and up-regulated the expression of angiostatin. Lymphatic endothelial cell invasion and tube formation as well as the expression of VEGF-C were also suppressed by PROX1 knockdown. PROX1 knockdown suppressed tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In contrast, PROX1 overexpression enhanced tumor cell angiogenesis, lymphangiogenesis, proliferation, migration, invasion, and epithelial-mesenchymal transition. Levels of phosphorylated Akt, GSK3β, and MAPK were decreased by PROX1 knockdown and increased by PROX1 overexpression. PROX1 expression positively correlated with tumor size, extent of differentiation, lymphovascular invasion, depth of invasion, lymph node metastasis, stage, and poor survival. The mean microvessel density and Ki-67 labeling index values of PROX1-positive tumors were significantly higher than those of PROX1-negative tumors. However, there was no significant correlation between PROX1 expression and lymphatic vessel density. These results indicate that PROX1 influences tumor progression in colorectal cancer by regulating angiogenesis and tumor cell proliferation.     

食管鳞癌组织LSDl表达与预后相关性分析

目的：研究组蛋白赖氨酸特异性脱甲基酶1（1ysinespecificdemethylase1,LSDl）在食管鳞癌组织中的表达及其与临床病理因素的关系,并探讨其与预后的相关性。方法：收集2005—01—01—2006—12—31在福建省肿瘤医院胸外科接受食管癌三野根治术且术前未接受放疗或化疗的食管鳞癌患者135例。免疫组化检测135例食管鳞癌及其配对癌旁正常食管黏膜组织的LSDl表达水平。运用Y。检验分析肿瘤组织LSDl表达与临床病理因素的关系。运用Kaplan-Meier方法和Log—rank检验分析肿瘤组织LSDl表达与患者术后总生存时间的关系。采用Cox模型对食管癌患者预后相关因素进行多因素回归分析。结果：食管鳞癌组织LSDl强阳性表达率为53．3％,在正常食管黏膜组织中为7．6％,差异有统计学意义,x2=9．016,P=0．002。LSDl高表达与性别（x2=0．396,P=0．546）、年龄（x2=2．530,P=0．123）、T分期（x2=1．264,P=0．286）、淋巴结转移（x2=1．136,P=0．343）、TNM分期（x2=0．396,P=0．546）和分化（x2=0．415,P=0．537）无显著相关性,而与生存时间是否超过5年（x2=6．699,P=0．013）显著相关。Cox多因素回归分析显示,淋巴结转移（p=0．001）、肿瘤浸润深度（P=0．004）和LSDl表达水平（P=0．020）是食管鳞癌患者的独立预后因素。生存分析提示,LSDl强阳性组患者预后明显差于LSDl弱阳性组患者,P=0．008。亚组分析显示,在有淋巴结转移的患者中,肿瘤LSDl强阳性与患者预后相关,P=0．014;而在无淋巴结转移的患者中,LSDl强阳性与预后无显著相关性,P=0373结诊．T-Snl在仓管鳞痛钼织申表达上调．其强阳性表达与不良预后相关。