The prognostic value of proliferating cell nuclear antigen,Ki-67 and nucleolar organizer region in transitional cell carcinoma of the bladder

Objectives: To investigate the value of proliferating cell nuclear antigen(PCNA), Ki-67 antigen labelling indices and nucleolar organizer region(NOR) score in relation to histological grade, stage, recurrence andprogression of the bladder tumor.Materials and methods: Tissue specimens from 77 bladder cancer patients(43 superficial, 34 invasive) were immunostained with PCNA and Ki-67 andstained with AgNOR. Thirteen specimens of normal bladder mucosa servedas controls.Results: In comparison to normal bladder mucosa the values of the threeindicators were significantly greater (p < 0.001). There was a significantrelationship between PCNA, Ki-67 indices, AgNOR scores and grade andstage of the tumor (p < 0.001). All indicators also correlated with each other(p < 0.001). The Kaplan-Meier curves for recurrence-progression freesurvival revealed that patients with a PCNA labelling index >36.22%, Ki-67labelling index >29.68% and AgNOR score > 3.34 had a worse prognosis thanthose with <36.22%, <29.68% and <3.34, respectively.Conclusions: PCNA, Ki-67 indices and AgNOR scores correlated with eachother and with tumor grade and stage. These proliferation markers maygive objective and accurate information about the biological behavior ofbladder transitional cell carcinoma.     

膀胱移行细胞癌增殖细胞核抗原表达的研究

采用免疫组化ＬＳＡＢ法对４８例膀胱移行细胞癌增殖细胞核抗原（ＰＣＮＡ）进行检测，发现ＰＣＮＡ增殖指数随肿瘤分级的升高而增高，浸润生长肿瘤ＰＣＮＡ增殖指数明显高于乳头状生长者（Ｐ＜０．００１），ＰＣＮＡ高表达组（增殖指数＞５０％）预后明显差于ＰＣＮＡ低表达组（增殖指数≤５０％）。结果表明ＰＣＮＡ可作为膀胱移行细胞癌恶性程度及预后指标之一。     

血管生成素-2在膀胱移行细胞癌中的表达及意义

目的　初步探讨血管生成素 2 (Ang 2 )在膀胱移行细胞癌组织中的表达及其与临床分期、病理分级的关系。方法　应用免疫组织化学S P法检测 4 3例初治膀胱癌及 2 8例正常膀胱组织中的Ang 2表达水平 ,并与临床资料对照进行统计分析。 结果　正常膀胱组织中未见Ang 2阳性染色 ;4 3例膀胱移行细胞癌中Ang 2阳性染色者 2 1例 ,Ang 2在许多膀胱癌细胞和癌组织中微血管内皮上呈强阳性染色 ,且染色率随膀胱癌病理分级、临床分期的上升而升高 (P <0 .0 5 )。结论　①Ang 2促进肿瘤新生血管形成 ,参与膀胱癌的发生和发展。②Ang 2的表达与膀胱移行细胞癌的临床分期、病理分级正相关。     

细胞周期蛋白D1在膀胱移行细胞癌中表达的意义

目的　探讨细胞周期蛋白Ｄ１（ｃｙｃｌｉｎ Ｄ１） 与膀胱移行细胞癌（ＴＣＣ） 生物学行为的关系。　方法　应用免疫组化法检测７１ 例膀胱ＴＣＣ 组织中ｃｙｃｌｉｎ Ｄ１ 的表达。　结果　３９ 例（５４ ．９％ ）ＴＣＣ 中ｃｙｃｌｉｎ Ｄ１ 呈阳性表达,其中Ｇ１ １１ 例（６８－８ ％ ）、Ｇ２ ２３ 例（６０－５ ％ ）、Ｇ３ ５ 例（２９－４ ％ ） 。３２ 例为胞核阳性,７ 例为胞浆阳性,其中Ｇ２ ３ 例,Ｇ３ ４ 例。６０ 例初发者阳性３５ 例（５８－３ ％ ） ,１１ 例再发者阳性４ 例（３６－４％ ） 。　结论　膀胱ＴＣＣ 是ｃｙｃｌｉｎ Ｄ１ 高表达的肿瘤类型之一,ｃｙｃｌｉｎ Ｄ１ 的过表达是膀胱癌发生过程中的早期事件,其与肿瘤病理分级显著相关,再发性ＴＣＣ 中表达有减少趋势,胞浆阳性代表着更高的恶性潜能     

Plasmacytoid transitional cell carcinoma of the urinary bladder

A case of rare plasmacytoid transitional cell carcinoma of the urinary bladder in a 60-year old man is described. The presence of end-stage disease did not allow for any efficacious therapy. Immunohistochemistry showed the tumor cells to be reactive for epithelial markers and syndecan-1 (CD138).     

Comparative assessment of proliferating cell nuclear antigen immunostaining and of nucleolar organizer region staining in transitional cell carcinomas of the urinary bladder. Correlation with other conventional prognostic pathologic parameters.

The expression of two cell proliferation indices, the proliferating cell nuclear antigen (PCNA), using the monoclonal antibody PC-10 in the immunoperoxidase method, and the nucleolar organizer regions (NORs), using the colloid silver nitrate staining technique, was assessed in formalin-fixed paraffin-embedded material of 50 transitional cell urinary bladder carcinomas. A relationship was found between the histologic grade and each of the two indices used. A significant difference was observed, particularly between carcinomas of grade II and III (p < 0.001). A relationship was also demonstrated between each of PC-10 and AgNOR scores and the clinical stage, but it was attributed mostly to the close correlation of the latter with the histologic grade of these tumors. The linear correlation coefficient between PC-10 and AgNOR scores was 0.757 (p < 0.001). Our results suggest that PC-10 and AgNOR scores may be important prognostic indices in urinary bladder cancer.     

The prognostic relevance of nuclear Feulgen DNA in transitional cell carcinoma of the urinary bladder. A long-term follow-up study

Feulgen DNA cytophotometry yielded prognostically significant information about the long-term relative survival in 123 patients with bladder cancer, even if subgroups with comparable T categories were compared. Patients with diploid tumours generally had a more favourable outcome than those with non-diploid ones. The percentage of tumour DNA stemline values was an additional prognostic parameter for diploid T1 tumours. It is suggested that DNA cytometric results ought to have an influence on the treatment of patients with bladder cancer.     

前列腺干细胞抗原在膀胱移行细胞癌中的表达及其临床意义

目的 采用量子点荧光标记技术观察前列腺干细胞抗原在膀胱移行细胞癌中的表达.方法 52例膀胱移行细胞癌手术标本,其中病检提示为表浅膀胱癌34例,侵犯肌层的有18例,所有标本行量子点荧光标记,每张设置阴性对照,实验后1个月内,在4个时间点对阳性部位荧光强度分4个等级做出判断.结果 在肿瘤细胞膜上出现一圈橙红色的荧光,细胞质和细胞核无荧光表达,阴性片表现为组织自身激发的绿色荧光,两者对照区别明显.这种阳性表达在表浅膀胱肿瘤中达到97.1%,在侵犯肌层的肿瘤中为77.8%,在病理级别为Ⅱ级的肿瘤中强阳性表达率为43.3%,Ⅲ级的强阳性表达率为59.1%.荧光强度在2周内无明显变化,到1个月时标本荧光强度有不同程度减弱,没有了荧光强度为"卅"的标本,除了4例标本荧光强度衰减为"0"外,其余仍在肉眼可识别范围内.结论 前列腺干细胞抗原是膀胱移行细胞癌有价值的瘤标,特别是对高级别表浅肿瘤敏感性高,可用于临床早期诊治和监测复发.     

The value of nuclear area as a prognostic factor in T1 papillary transitional cell carcinoma of the bladder.

In a series of 131 T1 papillary transitional cell carcinomas of the bladder, the nuclear areas of 100 nuclei (50 from the external papillary zone and 50 from the internal papillary zone) were measured. An attempt was made to correlate retrospectively the value of the mean nuclear area with histological grade and with survival. A higher value was obtained for the mean nuclear area of the internal papillary zone than for that of the external papillary zone. A better survival rate was found after 10 years' follow-up for those tumours whose mean nuclear area in the internal papillary zone was < or = 28 microns2, which suggests that it is in this zone that the nuclear area should be measured. A correlation was observed between the increase in the mean nuclear area value and higher histological grade.     

增殖细胞核抗原在脑胶质瘤中的表达

目的　探讨增殖细胞核抗原 (PCNA)在不同类型胶质瘤细胞中的表达 ,以及与复发、预后的关系。方法　应用抗 PCNA单克隆抗体 (小鼠IgGza型 ) ,对 61例脑胶质瘤患者病理切片行免疫组织化学染色 ,不同类型胶质瘤PCNA标记指数进行差异分析。结果　不同类型胶质瘤的PCNA标记指数 (LI)不同 ,随着胶质瘤恶性程度增高而增大 ,两者呈显著正相关 (r =0 .895 ,P <0 .0 1) ,各级别间LI的差异非常有显著性 (P <0 .0 1) ;死亡组与存活组间LI差异有显著性 ;肿瘤首发与否、性别、年龄组间差异无显著性 ;恶性程度、PCNA标记指数和放疗与否与预后相关 (P <0 .0 5 )。结论　PCNA可以作为提示胶质瘤预后的指标 ,对确定胶质瘤的生物学特性和肿瘤的分级有指导作用。不同恶性程度胶质瘤间LI差异有显著性 ,与恶性程度正相关 ,与胶质瘤的预后关系密切 ,PCNA的过度表达提示肿瘤恶性程度高 ,预后差。     

Combination of blood group ABH antigen status and DNA ploidy as independent prognostic factor in transitional cell carcinoma of the urinary bladder

The prognostic value of DNA ploidy and blood group (ABH) antigen reactivity was studied in a consecutive retrospective study of 230 patients with primary transitional cell carcinoma of the urinary bladder. In 195 cases the DNA ploidy and ABH reactivity could be assessed in paraffin-embedded tissue. Early progression (in the first 3 years) occurred in 2% of the patients with diploid ABH positive tumours and in 31% of those with aneuploid ABH negative tumours. The 5-year survival rates corrected for intercurrent mortality were 95 and 56% respectively. In a Cox multivariate analysis, T category, age at diagnosis and histological grade emerged as significant independent prognostic indicators of bladder cancer death, whereas ABH reactivity and DNA ploidy had no significant independent value. However, if the combination of ABH reactivity and DNA ploidy was included in the Cox model, this and T category were independent predictors. When this Cox model was applied to assess the risk of progression, the only independent prognostic factor was the combination of ABH reactivity and DNA ploidy.     

Metastases from transitional cell carcinoma of urinary bladder

In 107 patients who died of metastatic transitional cell carcinoma, the most common sites for metastases at necropsy were the lymph nodes, liver, lung, bone, and adrenal gland. Metastases first were documented clinically in multiple-organ sites in one third of the patients; solitary metastases were present in only 9 patients at necropsy. The mean duration of survival for patients was thirteen months from the diagnosis of the primary tumor. The metastatic lesion(s) generally were evident clinically within eleven months of the primary diagnosis; death ensued usually within three months. Our finding that the majority of patients presented initially with highgrade tumors suggests that a high-grade lesion, regardless of its clinical stage, warrants early aggressive therapy.     

膀胱癌中bcl-2和p16基因的表达与预后的关系

目的 探讨ｂｃｌ－２和Ｐ１６基因蛋白在膀胱癌的表达与预后的关系。方法 采用ＳＡＢＣ法对５１例膀胱癌组织和５例正常膀胱粘膜行ｂｃｌ－２和Ｐ１６基因表达的检测。结果 ｂｃｌ－２在膀胱癌的阳性表达率为８０．２％,生存组和死亡组之间比较差异有显著性意义。Ｐ１６在膀胱癌在阳生表达率为５０．９％。５例正常膀胱粘膜均阳性,两者比较有显著性意义。在病理分级、临床分期和预后的总样本率中比较差异有显著性意义;即随病理     

K-Ras mutation in transitional cell carcinoma of urinary bladder

In the present study it was aimed to investigate the frequency of K-RAS mutation in the human bladder transitional cell carcinoma. For thispurpose, tissue specimens obtained from the patients with bladder tumors.Genomic DNAs were isolated and then PCR-SSCP analysis of K-RAS genewere performed. A heterozygous deleted mutation was detected in K-RAS oncogene (exon 2) in agorose gel electrophoresis in one patient andpoint or substitution mutations are detected using single strandconformational polymorphism (SSCP) in other different patients withbladder cancer (4/14). In conclusion, the frequency of K-RAS mutationis not rare and the role of this mutation in oncogenesis and in infiltrationof the urinary bladder wall needs to be confirmed in a larger study.     

一氧化氮合成酶在膀胱癌中的表达及意义

目的　了解三种类型一氧化氮合成酶 (NOS)在膀胱癌中的表达情况 ,探讨其与肿瘤发生发展的关系。　方法　对 2 5例开放手术切除的膀胱癌组织标本进行三种NOS免疫组织化学染色 ,自动图像分析仪对染色程度分级 ;6例肾移植供体正常膀胱组织标本作为对照。　结果　诱导型NOS(iNOS)在肿瘤上皮细胞呈阳性表达 ,在正常膀胱移行细胞不表达或仅微弱表达 (P <0 .0 5)。内皮细胞型NOS (eNOS)在肿瘤基质毛细血管内皮细胞中的表达阳性率 1 0 0 % ,高于对照组中的 67%。两组标本中神经型NOS(nNOS)表达部位及强度相似。统计学分析显示iNOS和eNOS表达与肿瘤分级、分期无明显相关性 ,P均 >0 .0 5。　结论　iNOS及eNOS在膀胱癌的高表达可能与肿瘤的发生发展有关。     

Epithelial membrane antigen as an immunohistochemical marker for transitional cell carcinoma of the urinary bladder

Epithelial membrane antigen (EMA) was immunohistochemically localized in transitional cell carcinomas of the bladder to clarify EMA staining pattern's relationship to the histological grading and staging of tumors and patient prognosis. Formalin-fixed, paraffin-embedded sections from 101 patients with bladder carcinoma were stained by the indirect immunoperoxidase method. In the lower histological grade and stage of transitional cell carcinoma, the localization of EMA was restricted to the luminal surface of the superficial cells. Membrane and cytoplasmic staining of EMA was frequently found in the intermediate and basal layers of the tumor cells, and the incidence of cytoplasmic staining increased with advancing grade and stage. Stromal staining was frequently observed in cases of higher grade and stage. In addition, these distribution patterns of EMA were well correlated with patient survival. Thus, we differentiated three types of EMA distribution: a luminal type, with very good prognosis; a cytoplasmic type, with fair prognosis; and a stromal type, with relatively poor prognosis. These findings suggest that EMA distribution in bladder cancer could be a valuable indicator for histological grading or staging in pathological diagnosis and for predicting the survival of bladder cancer patients.