膀胱尿路上皮癌中LRG1和TGF-β1的表达及临床病理意义

目的 探讨富亮氨酸α2糖蛋白1（leucine-rich alpha-2-glycoprotein 1, LRG1）及转化生长因子beta 1（transforming growth factor-beta 1, TGF-β1）在膀胱尿路上皮癌（bladder urothelial carcinoma, BUC）组织中的表达及意义。方法 采用免疫组化SP法检测LRG1、TGF-β1及Ki-67在64例BUC组织及25例癌旁组织中的表达,分析LRG1、TGF-β1在各组间表达的差异及相关性。结果 LRG1在BUC组织中强阳性27例（42.19%）,癌旁组织中强阳性仅2例（8.00%）,两组相比差异有统计学意义（P<0.05）;TGF-β1在BUC组织中阳性49例（76.56%）,在癌旁组织中阳性10例（40.00%）,差异有统计学意义（P<0.05）;相关性分析显示,LRG1与TGF-β1表达呈正相关（r²=0.658 2,P<0.05）;LRG1、TGF-β1表达均与BUC病理学分级、浸润深度及Ki-67增殖指数相关（P<0.05）。结论 ...     

膀胱尿路上皮癌HER2表达及临床病理分析

目的 探讨膀胱尿路上皮癌(bladder urothelial carcinoma, BUC)中HER2的表达情况,并分析其临床意义。方法 收集膀胱非浸润性低级别BUC 27例、非浸润性高级别BUC 5例、浸润性高级别BUC 60例,采用免疫组化MaxVision法法检测各组织样本中HER2蛋白的表达,并分析HER2表达与临床病理特征的关系。通过GEPIA数据库或直接在肿瘤基因组图谱(The Cancer Genome Atlas, TCGA)中分析HER2(ERBB2)表达与BUC的关系。结果 浸润性高级别BUC中HER2 2+/3+表达率(26.67%,16/60)显著高于非浸润性低级别BUC(7.41%,2/27)和非浸润性高级别BUC(0,0/5)(P<0.05)。多灶性浸润性高级别BUC中HER2 2+/3+表达率(75.00%,6/8)显著高于单灶性患者(19.23%,10/52)(P<0.05)。各组织学亚型中HER2 2+/3+表达率差异有统计学意义(P<0.05),其中普通型为30%(6/20)、腺样分化型为57.14%(4/7)、微乳头型为66.6...     

膀胱尿路上皮癌MMP-2表达及其与FAK、p53、bcl-2、Ki-67的关系

目的 比较不同分化和浸润程度膀胱尿路上皮癌MMP—2表达及其与FAK、p53、bcl—2和Ki—67的关系。方法 采用免疫组化EnVision法对83例膀胱尿路上皮癌和68例非肿瘤尿路上皮，进行MMP—2、FAK、p53、bcl—2和Ki—67的表达检测。结果 MMP—2在肿瘤组织中的表达显著高于非肿瘤性移行上皮，其表达强度随肿瘤分化程度降低和浸润深度增加而显著增强。分化差和浸润性膀胱癌中FAK和p53表达增强，并与MMP—2表达呈正相关；分化差膀胱癌中Ki—67表达增强而bcl—2表达丢失，Ki—67与MMP—2表达呈正相关。结论 在膀胱尿路上皮癌的进展和分化过程中，肿瘤分化程度越低，肿瘤细胞分泌MMP—2越多，其浸润和转移的能力也越强。FAK、p53、Ki—67和bcl—2不但与肿瘤细胞的生长密切相关，还可能直接或间接地参与了MMP—2的调控。     

膀胱尿路上皮癌中LC3B与SQSTM1的表达及其临床意义

目的 探讨微管相关蛋白1轻链3β(microtubule-asso-ciated protein 1 light chain 3β,LC3B)及选择性自噬接头蛋白1(sequestosome 1,SQSTM1)在膀胱尿路上皮癌组织中的表达及其临床意义.方法 采用免疫组化MaxVision法检测LC3B与SQSTM1在4...     

miR-1在膀胱尿路上皮癌中的表达及其功能

目的研究miR-1在膀胱尿路上皮癌中的表达和临床意义,探讨miR-1在膀胱癌发病的作用。方法应用real-time PCR方法分别检测60例配对的新鲜膀胱尿路上皮癌及癌旁正常组织中miR-1的表达,统计分析miR-1表达差异与临床病理因素间的关系,应用CCK8法检测miR-1对膀胱癌T24细胞增殖能力的影响。结果miR-1在膀胱癌组织较癌旁正常组织中表达水平显著降低,而且肌层浸润性膀胱癌(T2-T4)患者组织中的miR-1表达显著低于非肌层浸润性膀胱癌组织(Ta-T1)。miR-1异常低表达与膀胱癌复发或转移、临床分期及病理分级密切相关,miR-1能够抑制膀胱癌T24细胞的增殖能力。结论miR-1在膀胱癌的发病过程中可能发挥着重要作用,可能成为未来膀胱癌治疗的新靶点及预后预测因子。     

膀胱浆细胞样尿路上皮癌1例

患者男性,70岁.无明显诱因出现肉眼血尿4个月余,伴尿频、尿痛,遂于2019年4月就诊于我院.男性泌尿系超声示膀胱壁低回声伴环状钙化,增强CT示膀胱左侧后壁局部不均匀增厚隆起(图1);腹膜后大血管旁多发淋巴结肿大.膀胱镜检查见膀胱左侧壁有一宽基息肉状新生物,膀胱内广泛滤泡样及鱼鳞样改变,侵及膀胱颈口及双侧输尿管开口.     

弥漫大B细胞淋巴瘤中PD-1、PD-L1的表达

目的探讨弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中程序性死亡受体-1(programmed death-1,PD-1)及程序性死亡配体-1(programmed death-ligand 1,PD-L1)的表达及临床意义。方法采用免疫组化法检测184例DLBCL组织中PD-1、PD-L1的表达,分析两者表达与DLBCL临床病理特征的关系。结果 184例DLBCL中肿瘤细胞PD-1、PD-L1阳性率分别为1. 63%、43. 48%;微环境细胞PD-1、PD-L1阳性率分别为11. 41%、26. 09%。肿瘤细胞及微环境细胞PD-1的表达与患者性别、年龄、Hans分型、CD5、EBER、ALK以及CD30的表达差异均无显著性(P均 0. 05)。非生发中心B细胞样(nongerminal center B-cell-like,non-GCB)型DLBCL肿瘤细胞(47. 55%)及微环境细胞(31. 47%)中PD-L1的阳性率高于生发中心B细胞样(germinal center B-cell-like,GCB)型DLBCL肿瘤细胞(29. 27%)及微环境细胞(7. 32%)(P均0. 05); EBV+DLBCL肿瘤细胞(75. 00%)及微环境细胞(58. 33%)中PD-L1的阳性率高于EBV-DLBCL肿瘤细胞(40. 74%)及微环境细胞(24. 07%)(P均0. 05); CD30+DLBCL(66. 67%)微环境细胞中PD-L1的阳性率高于CD30-DLBCL微环境细胞(27. 00%)(P=0. 005)。结论 PD-L1在non-GCB型以及EBV+DLBCL肿瘤细胞及微环境细胞中有更高的阳性率;且PD-L1在CD30+DLBCL微环境细胞中有更高的阳性率。     

膀胱癌组织中DMBT1基因的表达及临床意义

目的探讨膀胱癌中脑恶性肿瘤缺失基因1(DMBT1)的表达及其与肿瘤生物学行为的关系。方法采用RT-PCR和免疫组化SP法检测70例膀胱癌组织和12例正常膀胱组织中DMBT1 mRNA及蛋白的表达。结果膀胱癌组织中DMBT1 mR-NA和蛋白的表达水平低于正常膀胱组织(P<0.05),随着病理分级和临床分期的升高,DMBT1 mRNA和蛋白的表达水平明显下调(P<0.05)。DMBT1在有淋巴结转移的癌组织中表达明显低于在无淋巴结转移癌组织中的表达(P<0.05)。结论 DMBT1基因在膀胱癌组织中存在表达缺失和低表达,提示DMBT1基因在膀胱癌的发生、发展中可能具有抑癌基因的作用。     

基于免疫组化的膀胱浸润性尿路上皮癌的分子分型

目的 探讨用免疫组化法对膀胱浸润性尿路上皮癌进行分子分型的可操作性诊断方法和标准.方法 对197例膀胱浸润性尿路上皮癌行CK7、GATA3、FOXA1、CK20、CK14、CD44、CK5/6、p53、Ki-67等9种尿路上皮癌常用免疫组化染色,分析各项免疫组化标记表达的相关性,以及与各组织学变异的相关性,从中选择可用...     

Beclin 1 and bcl-2 expressions in bladder urothelial tumors and their association with clinicopathological parameters

Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation, as well as in the development and progression of cancer. The aim of this study was to examine the expression of beclin 1 and bcl-2 in bladder urothelial tumors, and to investigate the relationship between these two markers and clinicopathological parameters. Our study included 84 bladder urothelial tumors and 10 non-tumoral bladder tissues. Immunohistochemistry was performed on tissue microarray (TMA) sections and was evaluated semiquantitatively on the basis of the percentage of positively stained cells (proportion) and staining intensity. A significant association was found between the expression score of beclin 1 and pT stages of the urothelial tumors (p = 0.012). Also, the level of beclin 1 expression inversely correlated with histological grade and pT stages (p = 0.009, r = −0.284; p = 0.001, r = −0.361, respectively). The bcl-2 expression level positively correlated with histological grade and pT stages of the urothelial tumors (p = 0.026, r = 0.243; p < 0.0001, r = 0.491, respectively). In addition, the level of beclin 1 expression tended to be inversely correlated with the bcl-2 expression level in urothelial tumors (p = 0.055, r = −0.210). According to our data, down-regulation of beclin 1 expression and also bcl-2 overexpression seem to play an important role in the progression and aggressiveness of bladder urothelial tumors.     

膀胱乳头状尿路上皮肿瘤中CD10和CK20的表达

目的探讨CD10与CK20在膀胱乳头状尿路上皮肿瘤中的表达及临床病理意义。方法以19例正常尿路上皮为对照,采用免疫组化法检测74例膀胱乳头状尿路上皮肿瘤中CK20和CD10染色分布模式和强度以及二者之间的关系。结果CD10与CK20的阳性率分别为51.4%和54.4%,两者的染色分布和强度差异无显著性(P0.05)。CK20的染色分布模式在尿路上皮乳头状瘤(urothelial papilloma,UP)和非浸润性乳头状尿路上皮癌(non-invasive papillary urothelial carcinoma,NIPUC)中差异有显著性(P0.05)。CD10与CK20的染色强度整体比较差异有统计学意义(P0.05),且UP、低度恶性潜能未定的乳头状尿路上皮肿瘤(papillary urothelial neoplasm of law malignant potential,PUNLMP)与NIPUC组间相比差异均有统计学意义(P0.05)。两者联合检测阳性率达74.3%,癌组织中阳性率为84.9%。结论 CD10与CK20在膀胱乳头状尿路上皮肿瘤中的表达极其相似,联合使用明显提高阳性率;对鉴别尿路上皮乳头状肿瘤表浅病变的类型以及该类肿瘤的良恶性有意义。     

RIN1在人膀胱尿路上皮癌中的表达

目的研究RIN1在人膀胱尿路上皮癌中的表达。方法分别应用免疫蛋白印迹技术和实时定量PCR技术检测RIN1蛋白和RIN1 m RNA在人膀胱尿路上皮癌及癌旁组织中的表达。结果 Real-time PCR结果发现,在15对新鲜的膀胱尿路上皮癌及癌旁组织中,有12对的癌组织中RIN1表达高于癌旁组织。在膀胱尿路上皮癌组织中,RIN1的m RNA表达平均倍数为10.61±5.42,癌旁组织中,RIN1的m RNA平均倍数为4.31±1.77,P0.05。Western blot法结果认证了RIN1在膀胱尿路上皮癌组织中的表达是升高的。结论 RIN1在膀胱尿路上皮癌组织中的m RNA和蛋白的表达水平高于癌旁组织。     

Expression and function analysis of indoleamine 2 and 3-dioxygenase in bladder urothelial carcinoma

Indoleamine 2, 3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan metabolism inducing immune tolerance of tumors. The purpose of this study is to investigate IDO expression and its prognostic significance in bladder urothelial carcinoma (BUC). In this study, immunohistochemical staining for IDO expression in BUC tissues (n = 84) and normal bladder tissues (n = 22) was performed. The mRNA expression levels of IDO in BUC and normal bladder were analyzed by quantitative RT-PCR. Survival analysis was performed for the correlation of IDO expression and clinicopathological factors with disease-free survival. Positive expression of IDO was found in 48 of 84 cases in BUC tissues and was significantly correlated with histological classification, histological grade and TNM stage. While IDO expression in normal bladder tissues was expressed in only 4 of 22 (18.2%) cases. Moreover, IDO mRNA levels of BUC were significantly higher than that of normal bladder. We also found that IDO, histological grade and TNM stage were closely associated with DFS. These results indicated that IDO was related to the progression of BUC and might be one of the crucial prognostic factors for BUC.     

Prognostic value of immunohistochemical expression profile of epidermal growth factor receptor in urothelial bladder cancer

We studied epidermal growth factor receptor (EGFR) expression profile in urothelial bladder carcinoma (UBC) which is a complex and heterogeneous disease with a large spectrum of histological aspects and deadly potential. Using immunohistochemistry (IHC), all GI tumors and pTa cases showed a low expression profile of EGFR. However, we note that when the stage of disease is advanced, tumors over-express EGFR. Indeed, 5% and 25% of GII and GIII tumors over-expressed EGFR, respectively. Further, 0% of pTa, 9,5% of pT1, 15% of pT2, 50% of pT3, and 90% of pT4 tumors were shown to be high EGFR expression (HEE). Moreover, we found a statistically significant correlation between the EGFR over-expression and grade and stage (P < 0.05). Thus, EGFR over-expression could be a potential prognostic marker to predict poor outcome in Tunisian patients with UBC.     

Comparability of PD-L1 immunohistochemistry assays for non-small-cell lung cancer: a systematic review

Programmed cell death ligand 1 (PD-L1) immunohistochemistry is used to determine which patients with advanced non-small-cell lung cancer (NSCLC) respond best to treatment with PD-L1 inhibitors. For each inhibitor, a unique immunohistochemical assay was developed. This systematic review gives an up-to-date insight into the comparability of standardised immunohistochemical assays and laboratory-developed tests (LDTs), focusing specifically on tumour cell (TC) staining and scoring. A systematic search was performed identifying publications that assessed interassay, interobserver and/or interlaboratory concordance of PD-L1 assays and LDTs in tissue of NSCLC patients. Of 4294 publications identified through the systematic search, 27 fulfilled the inclusion criteria and were of sufficient methodological quality. Studies assessing interassay concordance found high agreement between assays 22C3, 28-8 and SP263 and properly validated LDTs, and lower concordance for comparisons involving SP142. A decrease in concordance, however, is seen with use of cut-offs, which hampers interchangeability of PD-L1 immunohistochemistry assays and LDTs. Studies assessing interobserver concordance found high agreement for all assays and LDTs, but lower agreement with use of a 1% cut-off. This may be problematic in clinical practice, as discordance between pathologists at this cut-off may result in some patients being denied valuable treatment options. Finally, five studies assessed interlaboratory concordance and found moderate to high agreement levels for various assays and LDTs. However, to assess the actual existence of interlaboratory variation in PD-L1 testing and PD-L1 positivity in clinical practice, studies using real-world clinical pathology data are needed.     

Micropapillary variant of urothelial carcinoma of the urinary bladder; a clinicopathological and immunohistochemical study

AIMS: To investigate whether prognosis in micropapillary urothelial carcinoma is related to the proportion of the micropapillary component (MPC), and to identify the immunohistochemical features of MPC. METHODS AND RESULTS: This study presents a clinicopathological analysis of 20 patients with micropapillary urothelial carcinoma of the bladder with cystectomy specimens for evaluation. Tumours were stratified on the extent of MPC: focal, <10%; moderate, 10-50%; extensive, >50%; and this was correlated with tumour stage and prognosis. Sixteen males and four females were aged 56-81 years (mean 69 years). All cases had high-grade morphology in the micropapillary carcinoma and typical urothelial carcinoma. All cases with extensive MPC (n = 4) were of a high pathological stage (pT3 or pT4) and died of disease (DOD) or other causes. Eighty percent with moderate MPC (eight of 10 cases) were pT3 or pT4 and 50% DOD or are alive with disease. Eighty-four percent with focal MPC (five of six cases) were pT1 or pTa. In high-stage cases, the most invasive component was MPC. High-stage cases had an 85% risk of being advanced at presentation with micropapillary carcinoma. All pT2 or lower stage cases had micropapillary carcinoma on prior transurethral resections of bladder tumour (TURB). High-stage carcinomas had 30% and 54%, respectively, of surface MPC and urothelial carcinoma in situ, in comparison with 85% and 28% in lower stage carcinomas. Immunohistochemical staining was similarly positive in MPC and typical urothelial carcinoma with cytokeratin (CK)7, CK20, epithelial membrane antigen, carcinoembryonic antigen and cytokeratin 34betaE12. CA125 staining was seen only in MPC in 43% of cases. CONCLUSIONS: Micropapillary urothelial carcinoma is a high-grade carcinoma in which the prognosis is related to the proportion and location of the MPC. Cases with moderate or extensive MPC are at high risk of being advanced at presentation. Cases with <10% MPC and surface MPC have a high chance of detection at an early stage. The morphology and immunohistochemical profile of the MPC suggest that it is a form of glandular differentiation in urothelial carcinoma.     

卵巢浆液性和黏液性肿瘤MUC1、MUC2的表达及其意义

目的探讨卵巢浆液性和黏液性肿瘤中黏蛋白MUC1、MUC2的表达与临床病理特征的相关性。方法免疫组化S—P法检测90例卵巢浆液性和黏液性肿瘤的黏蛋白MUC1、MUC2的表达,并对其中50例恶性病例作生存分析。结果（1）交界性与恶性卵巢肿瘤中黏蛋白MUC1的表达阳性率明显高于良性肿瘤,差异有显著性（P〈0．001）;黏蛋白MUC1与WHO病理分级、FIGO临床分期、大网膜转移显著相关（P〈0．05）。（2）黏蛋白MUC2与组织学类型、WHO病理分级相关（P〈0．05）。（3）黏蛋白MUC1与MUC2呈负相关（P〈0．05）。（4）对50例恶性浆液性和黏液性肿瘤进行的生存分析中,单因素分析显示：WHO病理分级、FIGO临床分期、大网膜转移、MUC1表达程度与预后相关（P〈0．05）,而多因素分析中只有FIGO临床分期、MUC1表达程度具有独立的预后意义（P〈0．05）,Kaplan—Meier生存曲线分析显示,Ⅲ、Ⅳ期较Ⅰ、Ⅱ期生存率差异有显著（P〈0．01）,MUC1阳性组和阴性组生存率差异有显著性（P〈0．01）。结论黏蛋白MUC1、MUC2与恶性卵巢浆液性和黏液性肿瘤的浸润、转移相关,Ⅲ、Ⅳ期肿瘤、MUC1强表达可作为恶性卵巢浆液性和黏液性肿瘤预后不良的可行性指标。     

膀胱癌中整合素连接激酶及相关信号转导通路分子的表达及意义

目的 探讨整合素连接激酶(integrin linked kinase,ILK)及相关信号转导通路分子在膀胱癌中的表达及其临床意义.方法 采用免疫组化SP法检测47例膀胱癌及25例癌旁组织中ILK、AKT及β-catenin的表达.结果 ILK、AKT和β-eatenin在膀胱癌和癌旁组织中的阳性率分别为53.19％和12.00％、44.68％和20.00％、48.94％和12.00％,且差异均有显著性(x2=11.651,x2=4.309,x2=9.650,P＜0.05).同时,ILK、AKT及β-catenin在高分化膀胱癌组中的表达明显低于低分化癌组,差异有统计学意义(P＜0.05).AKT、β-catenin和ILK在膀胱癌中的表达均呈正相关.结论 ILK、AKT及β-catenin的异常表达在膀胱癌的恶性进展中起重要作用,三者联合检测可能为揭示膀胱癌发生、发展的有关机制提供理论依据.ILK、AKT及β-catenin的异常表达与膀胱癌的临床病理分级密切相关,可能参与膀胱癌的发生、发展,联合检测有助于判断膀胱癌的恶性程度.