Towards a new WHO classification of renal cell tumor: what the clinician needs to know—a narrative review

In 1952, renal cell carcinomas had been divided into 2 categories—clear cell or granular cell—depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.     

Species differences in activating and inactivating enzymes related to the control of mutagenic metabolites

Microsomal monooxygenases catalyze the biosynthesis of epoxides from olefinic and aromatic compounds whilst microsomal epoxide hydratase and cytoplasmic glutathione S-transferases are responsible for their further biotransformation. Although catalytically very efficient the cytoplasmic glutathione S-transferases play, due to their subcellular localization, a minor role in the inactivation of epoxides derived from large lipophilic compounds and were, therefore, not included in this study. It was shown with such a lipophilic compound, benzo(a)pyrene, as a model substance and with liver enzyme mediated bacterial mutagenesis as biological endpoint that species and strain differences in epoxide hydratase and monooxygenases are reflected in very dramatic differences in mutagenicity of benzo(a)pyrene which varied from extremely potent to a degree which could easily be overlooked. In order to investigate whether the differences in enzyme activities were causally linked to the observed differences in mutagenicity, the enzyme activities were modulated by inhibition and induction. These manipulations were always accompanied by the corresponding changes in mutagenicity.It is concluded that species such as mice which possess high monooxygenase activity but very low epoxide hydratase activity are much more susceptible than man to those toxic effects which are mediated by metabolically formed epoxides which are substrates of epoxide hydratase. In this regard, it is especially noteworthy that mice possess a much lower hepatic epoxide hydratase activity than man.Presented at the Symposium Influence of Metabolic Activations and Inactivations on Toxic Effects held at the 18th Spring Meeting of the Deutsche Pharmakologische Gesellschaft, Section Toxicology, D-6500 Mainz, March 15, 1977     

使用多肿瘤标志物蛋白质芯片诊断系统(C-12)检测胃癌的临床价值

目的研究多肿瘤标志物蛋白芯片诊断系统用于胃癌的诊断价值。方法用多肿瘤标志物蛋白芯片诊断系统检测50例正常人,70例胃良性疾病及80例胃癌患者血清中十二种常见的肿瘤标志物:甲胎蛋白(AFP),癌胚抗原(CEA),神经元特异性烯醇化酶(NSE),糖原125(CA125),糖原153(CA153),糖原242(CA242),糖原199(CA199),前列腺特异性抗原(PSA),游离前列腺特异性抗原(f-PSA),铁蛋白(FER),β-人绒毛膜促性腺激素(β-HCG),人生长激素(HGH)的水平并进行统计学分析。结果80例胃癌患者血清有74例血清肿瘤标志物为阳性(阳性率为92.75%),70例良性胃疾病中10例肿瘤标志物为阳性(阳性率为14.28%),50份正常对照血清有1例血清肿瘤标志物为阳性(特异性为98%)。试验还发现部分胃癌患者血清中出现NSE,HGH,PSA,f-PSA。结论多肿瘤蛋白芯片的应用,对胃癌患者的术前肿瘤良恶性的判定有一定的临床应用价值。     

Next generation immunohistochemistry: Emerging substitutes to genetic testing?

The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently, immunohistochemistry (IHC) has emerged as a cost-effective strategy for detecting or inferring the presence of mutations in both tumors and the germline of patients presenting with tumors associated with hereditary cancer predisposition syndromes. In this review we discuss the use of novel IHC markers, including PRKAR1A, β-catenin, SDHB, fumarate hydratase and 2SC, HRASQ61R, BAP1, parafibromin and glucagon, which have either established applications or show promise for surgical pathologists to complement morphological or clinical suspicion of hereditary cancer predisposition syndromes. Specifically, we focus on Carney complex, familial adenomatous polyposis (FAP)-associated cribriform-morular variant of papillary thyroid carcinoma, familial succinate dehydrogenase-related pheochromocytoma/paraganglioma syndromes, hereditary leiomyomatosis and renal cell cancer (HLRCC), medullary thyroid cancer and Multiple Endocrine Neoplasia 2 (MEN2), BAP1 hereditary cancer predisposition syndrome, Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT), and Pancreatic Neuroendocrine Tumor Syndrome (Mahvash disease).     

出血性脑卒中临床预后因素的分析

目的探讨转化生长因子β1(TGF-β1)、神经元特异性烯醇化酶(NSE)等对出血性脑卒中后脑损伤和临床预后的影响。方法检测103例急性出血性脑卒中患者(出血性脑卒中组)血清TGF-β1、NSE水平并与68例健康体检者(健康对照组)比较,以3个月Barthel指数评分为临床预后指标,各因素进行单因素与多元回归分析。结果出血性脑卒中组患者急性期血清TGF-β1低于健康对照组(P<0.01)。NSE高于健康对照组(P<0.01)。单因素分析,TGF-β1、住院天数为出血性脑卒中患者神经功能恢复好的因素。NSE高、意识障碍程度重、出血量大、入院神经功能缺损评分高、空腹血糖高、外周血白细胞计数高、发热、最高体温高、患者年龄大、合并感染者神经功能恢复差。多元回归分析,血清TGF-β1、NSE、出血量、意识障碍程度、入院神经功能缺损评分影响出血性脑卒中患者临床预后。结论出血性脑卒中患者急性期血清TGF-β1明显下降;重症患者NSE显著增高。     

rr－烯醇化酶单克隆抗体双位点夹心ELISA的建立和临床应用

在自制的８株烯醇化酶（ＮＳＥ）ＭｃＡｂ中，经方阵排列滴定筛选出无交叉反应且效价较高的２株ＭｃＡｂ，用辣根过氧化物酶（ＨＲＰ）为标记物，建立了ＮＳＥ－ＭｃＡｂ双位点夹心ＥＬＩＳＡ。经直线回归方程、取代试验、阻断试验检验，该标准曲线近似直线关系，可测定标本中ＮＳＥ的范围为５～５０μｇ／Ｌ。对２３例小细胞肺癌（ＳＣＬＣ）（Ⅰ和Ⅱ期４例、Ⅲ期７例、Ⅳ期１２例）．３２例非小细胞肺癌（ＮＳＣＬＣ），２２例肺良性疾病（ＢＰＤ）和３６例健康体检者血清ＮＳＥ进行了测定，ＳＣＬＣ的阳性率为８２．６％（１９／２３），其中Ⅰ和Ⅱ期为５０％（２／４）；Ⅲ期为８５．７％（６／７），Ⅳ期为９１．７％（１１／１２）；ＮＳＣＬＣ的阳性率为３．１％（１／３２），ＢＰＤ阳性率为４．５％（１／２２）。ＳＣＬＣ的显著高于ＮＳＣＬＣ和ＢＰＤ（Ｐ＜０．０１）；ＳＣＬＣ的Ⅳ和Ⅲ期显著高于Ⅰ和Ⅱ期（Ｐ＜０．０１）。２３例ＳＣＬＣ经综合治疗后，完全缓解组和部份缓解组血清ＮＳＥ水平非常显著低于进展组和无改变组（Ｐ＜０．０１）。本文研究结果证明，ＮＳＥＭｃＡｂ双位点夹心ＥＬＩＳＡ具有灵敏、特异和简便快速的特点，对ＳＣＬＣ的血清学诊断有较高的灵敏度和特异性，对ＳＣ     

Multiple cutaneous leiomyomas leading to discovery of novel splice mutation in the fumarate hydratase gene associated with HLRCC

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant condition, which manifests as cutaneous leiomyomas (CL), uterine fibroids and renal cell cancer (RCC). We describe the case of a 53‐year‐old woman who presented with multiple CL with a novel heterozygous canonical splice site mutation in intron 9 of the fumarate hydratase (FH) gene IVS 9–1 G>C ( NM_000143.3 :c 1391–1 G>C) that was not detected on initial screening of a mutation hotspot but was picked up on sequencing the remaining exons and splice site junctions. This report highlights the importance of clinical suspicion in the diagnosis of HLRCC in the absence of a family or personal history of cancer and despite initial genetic testing being negative.     

肠道病毒中枢神经系统感染病儿免疫功能紊乱与神经元损害的相关性

目的通过检测肠道病毒（EV）中枢神经系统感染病儿脑脊液中白细胞介素-10（IL-10）、γ-干扰素（IFN-γ）及神经元特异性烯醇化酶（NSE）的水平,探讨EV引起病儿免疫功能紊乱的机制。方法收集2008年1月—2009年1月青岛大学医学院附属医院和滨州医学院附属医院临床诊断为无菌性脑膜炎、脑炎病儿的急性期脑脊液标本100例。采用逆转录聚合酶链反应（RT-PCR）方法,检测标本中的EV RNA;应用双抗体夹心ELISA法检测EV感染组和对照组脑脊液中IL-10、IFN-γ及NSE的表达水平。结果 100例急性期病儿脑脊液中,经RT-PCR和二次PCR共获得阳性结果78例（78.0%）;EV感染组IFN-γ的表达水平高于对照组（t=4.24,P〈0.01）,重症组高于轻症组（t=4.13,P〈0.01）;IL-10表达水平低于对照组（t=7.89,P〈0.01）,重症组低于轻症组（t=2.97,P〈0.01）;NSE表达水平高于对照组（t=7.02,P〈0.01）,重症组高于轻症组（t=2.79,P〈0.01）。EV感染组NSE与IFN-γ水平呈正相关（r=0.673,P〈0.05）,与IL-10水平呈负相关（r=-0.587,P〈0.05）。结论 IL-10和IFN-γ参与EV对中枢神经系统免疫损害的过程,并与神经元的损害程度密切相关。     

脑外伤患者血清NSE、Tau、S100、MMP-9水平与脑水肿相关性的研究

[目的] 探讨脑外伤患者血清神经烯醇化酶(NSE)、Tau蛋白、S100蛋白、基质金属蛋白酶9(MMP-9)与脑水肿的相关性.[方法] 选择2013年1月至2016年11月本院收治的96例颅脑外伤患者的临床资料,将其分为观察组,选择同期招募的60名健康者作为对照组,脑外伤患者于入院时、入院后d3和d7分别行头部CT检查评估脑水肿体积.采用ELISA法检测脑外伤患者入院当日的血清NSE、Tau、S100、MMP-9蛋白水平,所有健康对照在入选后亦检测相同指标.比较两组患者的血清NSE、Tau、S100、MMP-9蛋白水平,分析观察组脑水肿体积与各血清蛋白Pearson相关性.[结果] 观察组患者入院当日血清NSE、S100、MMP-9水平均高于对照组,差异均具有统计学意义(均P<0.05).对照组血清Tau蛋白水平高于观察组,但差异无统计学意义(P>0.05).入院时观察组患者的血清NSE、Tau、S100、MMP-9水平均与入院当天CT检测的脑水肿体积呈显著正相关性(均P<0.05);入院时血清S100、MMP-9水平与入院d3的脑水肿体积亦呈显著正性相关性(均P<0.05).入院时血清S100、MMP-9水平与脑水肿进展值呈显著正相关性.[结论] 血清NSE、Tau、S100和MMP-9水平可在一定程度上反映脑外伤后脑水肿的程度,并且MMP-9、S100还可提示脑水肿的进展可能,对评估患者受伤后脑水肿的情况具有参考价值.     

多种肿瘤标记物检测在肺癌诊断中的意义

【目的】探讨多种肿瘤标记物检测在肺癌诊断中的应用价值。【方法】本院接受治疗的50例肺癌患者为观察对象,同时选取48例肺良性病变者（肺良性病变组）以及42例健康体检者作为对照。观察三组对象血清肿瘤标志物癌胚抗原（CEA）、糖蛋白抗原 CA19‐9（ CA19‐9）、CA125和神经元特异性烯醇化酶（NSE）水平的差异及不同临床特征肺癌患者肿瘤标志物水平的差异。【结果】三组 CEA 、CA19‐9,CA125,NSE 等肿瘤标志物水平由高到低分别为肺癌组、肺良性病变组和健康对照组,且各组之间相比较差异具有显著性（P ＜0．01）;分化程度低、肿瘤直径≥5 cm 、有远处转移的肺癌患者其 CEA 、CA19‐9、CA125和 NSE 水平较高（P ＜0．05）,而不同年龄、性别的肺癌患者上述指标相比较差异无显著性（P ＞0．05）。【结论】患者血清 CEA 、CA19‐9,CA125,NSE 水平与肺癌的分化程度、转移情况密切相关,其检测结果有利于肺癌的早期发现和治疗,具有较好的应用价值。