膀胱癌原癌基因c－erbB－2蛋白产物的表达

采用免疫组化ＰＡＰ方法对６３例膀胱癌癌基因ｃ－ｅｒｂＢ－２表达产物进行检测，２９例显示表达阳性，且阳性率在恶性度低、浅表性肿瘤中较高，Ⅰ与Ⅲ级、１＋Ⅱ与Ⅲ级、Ｔｉｓ－Ｔ１与Ｔ２～Ｔ４比较均有显著性差异（Ｐ＜０．０５），表明ｃ－ｅｒｂＢ－２蛋白表达与膀胱癌细胞分化程度、浸润程度及预后关系不大。     

膀胱癌患者尿脱落细胞中细胞角蛋白20的表达及临床意义

目的　探讨膀胱癌患者尿脱落细胞中细胞角蛋白 2 0 (CK2 0 )的表达及临床意义。　方法　采用RT PCR方法检测 4 1例膀胱癌、2 0例其他泌尿系疾病患者及 10例正常人尿脱落细胞中CK2 0的表达。　结果　 10例正常人的尿脱落细胞均未表达CK2 0 ;2 0例非膀胱癌者中 3例表达CK2 0 ;4 1例膀胱癌患者中 37例表达CK2 0 ,三组间比较差别有显著性意义 (P <0 .0 1)。G1、G2 及G3膀胱癌的阳性率分别为 90 .2 % (2 3/2 5 )、88.8% (8/9)及 85 .7% (6 /7) ,三组比较差别无显著性意义(P >0 .0 5 )。　结论　CK2 0在膀胱癌患者尿脱落细胞中表达阳性率高 ,可用于膀胱癌的诊断及术后随访。     

Expression of c-erbB-2 gene product in urinary bladder cancer

Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer.     

c-myc oncoprotein levels in bladder cancer

Summary The protein coded by the oncogene c-myc, p62^c-myc, was measured using monoclonal antibodies and flow cytometry in nuclei derived from paraffin-wax sections of transitional cell carcinomas of the human bladder. Superficial disease (stages pTa and pT1) which did not recur within 5 years of diagnosis had significantly higher oncoprotein levels than those which did recur or were muscle-invasive (stage pT2 or greater) at presentation (P<0.01). These preliminary findings indicate that oncoprotein levels might have prognostic significance for bladder cancer.     

膀胱移行细胞癌c-myc癌基因蛋白表达的临床意义

目的：探讨膀胱移行细胞癌ｃ－ｍｙｃ癌基因蛋白表达的临床意义。方法：应用免疫组织化学ＳＰ方法检测５０例膀胱移行细胞癌标本（其中Ⅲ级１８例,Ⅱ级１６例,Ⅰ级１６例）中ｃ－ｍｙｃ癌基因蛋白。结果：Ⅲ级中ｃ－ｍｙｃ癌基因蛋白表达阳性率为９４．４％,Ⅱ级表达阳性率为７５．０％,Ⅰ级中表达阳性率为４３．７％,３组之间表达阳性率有显著性差异（Ｐ〈０．０１）。结论：膀胱移行细胞癌病理分化越低,ｃ－ｍｙｃ癌基因蛋白     

p53 expression in patients with advanced urothelial cancer of the urinary bladder

Study Type – Prognosis (inception cohort)
Level of Evidence 1b

OBJECTIVE

To test whether assessing p53 expression could improve the ability to predict disease recurrence and disease‐specific survival in a multi‐institutional cohort of patients with advanced urothelial carcinoma of the urinary bladder (UCB).

PATIENTS AND METHODS

The study comprised 692 patients with pT3–4 N0 or pTany N+ UCB treated with radical cystectomy and lymphadenectomy. The predictive accuracy (PA) was quantified using the 200 bootstrap‐corrected concordance index. The base model comprised age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of lymph nodes positive, concomitant carcinoma in situ, and adjuvant chemotherapy.

RESULTS

p53 expression was altered in 341 (49.3%) patients. In multivariable analyses, p53 expression was independently associated with disease recurrence (hazard ratio, 1.66; P < 0.001) and cancer‐specific mortality (hazard ratio 1.65, P < 0.001). Overall, adding p53 did not significantly improve the PA of the base model (recurrence +0.7%, P = 0.085, and cancer‐specific mortality +1.2%, P = 0.050). In the subgroups of pT3N0 (280) and pT4N0 (83) patients, p53 slightly improved the PA of the base model by a statistically significant degree (recurrence +1.7% and +3.6%, respectively; cancer‐specific mortality +1.9% and +3.5%, respectively; all P < 0.001). In 329 patients with pTany N+ disease p53 status did not improve the PA of the base model.

CONCLUSION

While assessing p53 expression has limited utility in patients with lymph node‐positive UCB, it marginally improves prognostication in patients with advanced non‐metastatic UCB. Integration of p53 into a panel of biomarkers might be necessary to capture a more accurate picture of the biological potential of advanced UCB.     

c-erbB-2和cox-2在乳腺癌中的表达及其意义

应用免疫组化技术 ,检测人乳腺良恶性疾病组织中c erbB 2和cox 2蛋白的表达 ,分析其与淋巴结转移、激素受体状态的关系。 40例乳腺癌组织中c erbB 2表达阳性率为 3 5 .0 %,淋巴结阳性及激素受体阴性者表达率显著高于无淋巴结转移及受体阳性者 (均P <0 .0 5 ) ;cox 2表达阳性率为 47.5 %,激素受体阴性者表达率显著高于受体阳性者 (P <0 .0 5 ) ,但与淋巴结转移无关 (P >0 .0 5 )。 10例良性乳腺疾病及 2例正常乳腺组织中无c erbB 2表达 ,仅有 1例乳腺囊肿病cox 2表达阳性 ,c erbB 2与cox 2的表达存在显著的相关性 (P <0 .0 5 )。提示c erbB 2和cox 2与乳腺癌的发生、转移及预后均有密切关系 ,同时进行两者的免疫组化检测对评估乳腺癌的预后及选择靶向治疗对象可能有意义。     

膀胱尿路上皮癌组织中HMGA2蛋白表达及其临床意义

目的 探讨高迁移率族蛋白A2(high mobility group protein A2,HMGA2)在膀胱癌组织中的表达情况,并分析其与临床病理特征及复发的关系.方法 膀胱尿路上皮癌标本148例,正常膀胱组织标本30例,采用免疫组织化学方法检测2组标本组织中HMGA2蛋白的表达,并结合临床资料进行分析.结果 正常膀胱组织中无HMGA2蛋白表达,肿瘤组织中随病理分级和分期增加,HMGA2蛋白相对表达量逐渐增高.HMGA2蛋白在G1、G2、G3组织中表达阳性率分别为21.3%、60.3%、82.1%,差异有统计学意义(P＜0.001).非肌层浸润性膀胱尿路上皮癌和肌层浸润性膀胱尿路上皮癌中HMGA2蛋白表达的阳性率分别为43.3%和72.7%,差异有统计学意义(P=0.003).随访2～95个月,复发64例,复发组与未复发组中HMGA2蛋白表达阳性率分别为54.7%和25.0%,差异有统计学意义(P=0.007).结论 HMGA2蛋白表达在膀胱癌组织中明显高于正常组织,HMGA2蛋白表达与膀胱癌的分级、分期、复发有关;与患者年龄、性别、肿瘤数目无相关性.检测HMGA2蛋白有助于膀胱癌的诊断及预后的评估.

Abstract：

Objective This study was to explore the expression and significance of HMA2 in bladder cancer , analyze its correlations to clinicopathologic and recurrence of bladder cancer. Methods The expression of HMGA2 protein in 148 specimens of bladder cancer and 30 specimens of normal bladder tissues was detected by immunohistochemtry, its correlations to clinicopathologic features was analyzed. Results There was no expression of HMGA2 protein in normal bladder tissues,while the expression level of HMGA2 protein was getting higher with the increase of tumor pathology grade and stage. The positive rate of HMGA2 protein was 21.3% in G1 bladder cancer, 60. 3% in G2 bladder cancer, 82.1% in G3 bladder cancer, its difference is significant (P＜0. 001). It was significantly lower in non-muscle invasive bladder cancer than in muscle invasive bladder cancer (43.3% vs 72. 7%, P=0. 003). The patients were followed up for 2～95 months, patients of recurrence was 64,HMGA2 protein expression was significantly higher in patients with recurrence than with non-recurrence (54.7% vs 25.0%, P=0. 007). Conclusions The expression of HMGA2 protein was highly in bladder cancer, the positive rate of HMGA2 protein expression was related with classification,TMN stage and recurrence, but not with sex, age, tumor number (P＞0. 05). The detection of the expression of HMGA2 protein is in favor of diagnosis and prognostic evaluation of bladder cancer.     

Proliferating cell nuclear antigen and c-erbB-2 oncoprotein expression in adenoid cystic carcinomas of the salivary glands.

BACKGROUND: Adenoid cystic carcinoma (ACC) of the salivary gland shows a variable clinical course. It would be helpful to discover reliable biologic markers in the management of patients with ACC. METHODS: We examined proliferating cell nuclear antigen (PCNA) and c-erbB-2 oncoprotein expression on 30 cases of ACC of the salivary glands. The immunohistochemical results, and size, location, and histologic grade of the tumors were compared with the clinical outcome of the patients. RESULTS: Mean PCNA positivity of ACCs was 15%, and was higher in solid than in cribriform/tubular areas. High PCNA value was significantly correlated with shorter disease-free and overall survival of the patients with ACC. c-erbB-2 overexpression was observed in only five cases, focally in cribriform/tubular areas. High histologic grade, which was determined by the presence of solid components, showed a trend toward shorter survival. Size and location of ACC were not associated with patient outcome. CONCLUSIONS: The present study indicates that PCNA score may be one of the most useful prognostic factor of ACC.     

抗凋亡基因bcl—2在膀胱肿瘤中的表达及意义

应用链菌素亲和素－过氧化物酶（ＬＳＡＢ）免疫组织化学技术对４９例膀胱肿瘤石蜡切片ｂｃｌ－２原癌基因蛋白的表达进行研究，结果显示，在各级（期）膀胱肿瘤中均为ｂｃｌ－２基因表达，随着肿瘤分级，分别的增加，ｂｃｌ－２基因表达增多，但无显著性差异（Ｐ〉０．０５），在〉５０岁以上患者中ｂｃｌ－２基因表达率明显高于≤５０岁者（Ｐ〈０．０５）。虽然在复发肿瘤和多发肿瘤及男性患者ｂｃｌ－２基因表达有增加趋势，但其     

Prognostic significance of co-expression of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer patients.

The expression of c-erbB-2 oncoprotein and epidermal growth factor receptor (EGFR) was examined by immunocytochemical and radioreceptor assays in 115 patients with primary breast cancer. In 48 of 115 patients (42%), the assays were found to be positive for the expression of c-erbB-2 oncoprotein, and, in 44 of 115 (35%) patients, the assays were positive for the expression of EGFR. There was no correlation between the expression of c-erbB-2 oncoprotein and EGFR. Clinical survey demonstrated that both c-erbB-2 oncoprotein expression and EGFR expression have independent prognostic values. Furthermore, when patients were divided into three groups on the basis of the expression of both c-erbB-2 oncoprotein and EGFR, those who were found to be positive for the expression of both c-erbB-2 oncoprotein and EGFR showed a worse prognosis than other groups. These results suggest that the combination of the expression of both c-erbB-2 oncoprotein and EGFR may be important in selecting patients who have a poor prognosis.     

Dysplastic urothelial changes in patients with bladder cancer

The authors treated 238 patients with urinary bladder tumours in 4 years. In each case the transurethral resection formed an integrae part of the treatment plan in the form of a diagnostic, curative or palliative TUR. The transurethral intervention in 152 cases was carried out with differentiated resection technique according to Bressel, in 137 cases mapping was also made of 9 different points. By this technique detailed information was obtained about the pathological lesion of the mucosa which appeared healthy by endoscopy in 122 patients. Precancerous lesions which can form the basis for later malignant epithelial proliferation were found in 50,9% of the patients. The number and severity of the dysplastic lesions showed close correlation with the histological differentiation grade of the tumour.     

肺癌肿瘤抑制因子1在膀胱尿路上皮癌中的表达

目的 探讨肺癌肿瘤抑制因子1(tumor supressor in lung cancer 1,TSLC1)与膀胱尿路上皮癌病理分级的相关性. 方法 免疫Balb/c雌性小鼠,通过脾细胞和骨髓瘤细胞融合技术制备TSLC1单克隆抗体,并测定效价;同时选取膀胱尿路上皮癌蜡块65例(低危组40例,高危组25例),正常膀胱黏膜20例,应用免疫组化检测TSLC1蛋白表达情况,由两位病理医生根据染色情况确定阴性(-)、弱阳性(+)、强阳性(++).利用SPSS 13.0软件对不同病理分级的TSLC1蛋白表达情况进行统计学分析. 结果 成功制备TSLC1单克隆抗体IgG1,测其效价为1∶100 000;免疫组化示细胞质、细胞膜显色.高危组TSLC1蛋白表达阴性为88%(22/25),弱阳性为12%(3/25);低危组TSLC1蛋白表达弱阳性为75%(30/40),阴性25%(10/40);正常膀胱黏膜移行上皮均为强阳性表达,三组间差异均有统计学意义(P＜0.05). 结论 TSLC1蛋白的表达与膀胱尿路上皮癌病理分级呈负相关,在评价肿瘤预后方面具有重要的临床参考价值,是膀胱肿瘤生物学行为中有价值的标志物之一.     

Subsequent upper urothelial cancer following bladder tumor

A total of 110 patients were treated with primary transitional cell carcinoma (TCC) of the urinary bladder from 1990 to 2000. During the follow-up period, which was for at least two years, four patients (3.6 percent) had subsequent upper urothelial cancer at an average of 61.5 months after initial treatment of the bladder tumor. Two of the four patients received transurethral resection several times, and the remaining two patients underwent radical cystectomy for the initial bladder tumor. The histopathological findings of subsequent upper urothelial cancer were almost the same as those for the initial bladder tumor. One patient had accompanying carcinoma in situ (CIS) and the other had adenocarcinoma with TCC. Since 1) high grade, 2) multiple, 3) recurrent and 4) occupational bladder tumors, 5) concomitant CIS, 6) vesicoureteral reflux and 7) tumor invasion of the intravesical ureters have been reported to be risk factors for developing subsequent upper urothelial cancer, patients with bladder tumors who have these risk factors should be followed-up closely.     

Association between pioglitazone and urothelial bladder cancer

The U.S. Food and Drug Administration and the European Medicines Agency have recently informed the public of a potential impact of pioglitazone (Actos) use on bladder cancer incidence. These recommendations are based on 2 recent large published cohort studies indicating a possible association between pioglitazone use and bladder cancer development. Currently, there is no urology literature on this subject. We present the current literature reporting the association between pioglitazone and bladder cancer.     

Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours

Background

Her2, an alias for the protein of v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), might be an attractive therapeutic target in metastasising bladder cancer. Genotype and phenotype of primary tumours and their metastases may differ.

Objectives

Determine Her2 status in both tumour components to better assess the potential of anti-Her2 therapies.

Design, setting, and participants

Histologic examination revealed lymph node metastases in 150 patients with urothelial bladder cancer clinically staged as N0M0. A tissue microarray was constructed with four tumour samples per patient: two from the primary tumour and two from nodal metastases. Her2 status was determined at the gene level by fluorescence in situ hybridisation (FISH) and at the protein level by immunohistochemistry (IHC).

Interventions

All patients underwent cystectomy and standardised extended lymphadenectomy.

Measurements

Overall survival was assessed according to HER2 gene status and protein expression in primary bladder cancers and lymph node metastases.

Results and limitations

Her2 amplification was significantly more frequent in lymph node metastases (15.3%) than in matched primary bladder cancers (8.7%; p = 0.003). Her2 amplification in primary tumours was highly preserved in the corresponding metastases as indicated by only one amplified primary tumour without amplification of the metastasis. There was a high concordance in HER2 FISH results between both samples from the primary tumour (κ = 0.853) and from the metastases (κ = 0.930). IHC results were less concordant (κ = 0.539 and 0.830). FISH and IHC results were poorly correlated in primary tumours (κ = 0.566) and metastases (κ = 0.673). While Her2 amplification in the primary tumour significantly predicted poor outcome (p = 0.044), IHC-based survival prediction was unsuccessful.

Conclusions

Her2 amplification in metastasising bladder cancer is relatively frequent, is homogeneous in each tumour component, and predicts early death. This suggests a high potential for anti-Her2 therapies. For patient selection, FISH might be more accurate than IHC.     

膀胱癌尿脱落细胞端粒酶活性检测及其临床意义

目的检测尿脱落细胞端粒酶活性并探讨其临床意义。方法应用改良的端粒重复序列扩增（ＴＲＡＰ）银染方法,分别对膀胱癌组织、正常膀胱组织,以及膀胱癌患者和非尿路上皮肿瘤患者的尿脱落细胞、膀胱冲洗液进行端粒酶活性检测。结果１２例正常膀胱组织均无端粒酶活性,４８例膀胱癌组织中４４例（９１．７％）端粒酶阳性。膀胱癌患者尿液及膀胱冲洗液中脱落细胞端粒酶阳性率分别为８３．３％（４０／４８）和８７．５％（４２／４８）。１２例分化良好（Ｇ１级）膀胱癌患者中,尿液和膀胱冲洗液中脱落细胞端粒酶阳性率分别为７５．０％（９／１２）和８３．３％（１０／１２）。结论尿脱落细胞端粒酶活性检测敏感性高,可用于膀胱癌的早期诊断和术后随访。