鼻咽癌p53 p21 WAF1和MDM2蛋白异常表达的临床意义

目的：探讨p53、p21^WAF1、MDM2蛋白在原发鼻咽癌（NPC）异常表达的临床意义。方法：采用LSAB法检测69例原发NPC组织中p53、p21^WAF1和MDM2蛋白的表达状况。结果：1）p53、p21^WAF1和MDM2蛋白在原发NPC组织的阳性表达率分别为79．7％、84．1％、和82．6％；高表达率分别为50．7％、46．4％和31．9％。2）p53蛋白的高表达率随TNM分期的升高而增多，P＝0．042。3）p53或MDM2蛋白高表达者的复发间期显著短于相应蛋白低表达／阴性者，分别P＝0．038和P＝0．002。4）p53和MDM2蛋白同时高表达者、MDM2蛋白高表达同时p21^WAF1蛋白低表达／阴性者的复发间期明显短于对照组，分别P＜0．001；p21^WAF1蛋白高表达同时p53蛋白低表达／阴性者、p53和MDM2蛋白同时低表达／阴性者的复发间期显著长于对照组，分别P＝0．002和P＝0．014。5）p53和MDM2蛋白高表达同时p21^WAF1蛋白低表达／阴性者的复发间期明显短于对照组，P＜0．001；p53和MDM2蛋白低表达阴性同时p21^WAF1蛋白高表达者的复发间期明显长于对照组，P＝0．002。结论：p53或MDM2蛋白高表达提示有促进NPC复发的作用，p21^WAF1蛋白高表达提示有抑制NPC复发的作用。单独检测p53或MDM2蛋白在原发NPC组织的表达情况可以和为预测NPC复发倾向和临床预后的参考指标；如同时检测p53、MDM2和p21^WAF1蛋白的两项或三项指标，预测意义更理想。     

结直肠癌中survivin、caspase-3、p21WAF1的蛋白表达及其意义

目的探讨结直肠癌中survivin、caspase-3和p21^WAF1的蛋白表达与临床病理参数的联系以及survivin与caspase-3和p21^WAF1蛋白表达之间的关系。方法采用免疫组织化学SP方法检测15例正常结直肠粘膜和62例结直肠腺癌标本中survivin、caspase-3和p21^WAF1的蛋白表达。结果结直肠腺癌与正常结直肠粘膜比较,survivin、caspase-3和p21^WAF1的蛋白表达差异均有显著性（P〈0.05）。survivin和caspase-3的蛋白表达与淋巴结转移无明显相关（P〉0.05）;而与分化程度均显著相关（P〈0.05）。survivin蛋白与Dukes分期相关（P〈0.05）;但caspase-3的蛋白表达与Dukes分期无关（P〉0.05）。p21^WAF1蛋白表达与分化程度、淋巴结转移和Dukes分期均显著相关（P〈0.05）。survivin蛋白分别与caspase-3、p21^WAF1蛋白表达之间均呈显著负相关（P〈0.01）。结论survivin、caspase-3和p21^WAF1蛋白在结直肠癌的发生和进展中都起着重要的作用。p21^WAF1基因与结直肠癌的恶性进展显著相关,此结论鲜见报道。     

ET-1和VEGF-C在喉癌中的表达及临床意义

目的：研究血管内皮素-1（ET-1）和血管内皮生长因子-C（VEGF-C）在喉癌组织中的表达规律,探讨两者与喉癌发生、发展和淋巴结转移的关系及在预后中的意义。方法：选择45例经病理确诊的喉癌组织为实验组,20例喉良性病变组织为对照组,免疫组化法和实时荧光定量PCR法检测ET-1和VEGF-C蛋白和mRNA的表达,5＇-核苷酸酶染色法（5＇-Nase）计数淋巴管密度（LVD）,CD34染色计数微血管密度（MVD）,并结合临床病理特征和生存资料进行相关分析。结果：喉癌淋巴结转移组ET-1、VEGF-C蛋白和mRNA表达显著高于未转移组（P〈0.05）,二者均显著高于良性喉组织（P〈0.01）。喉癌组织中ET-1蛋白表达与瘤内和瘤周LVD、MVD、淋巴结转移、淋巴管浸润、TNM临床分期显著相关（P〈0.05）,与年龄、性别、肿瘤部位及组织学分级无关（P〉0.05）。VEGF-C蛋白表达与瘤内和瘤周LVD、淋巴结转移、淋巴管浸润、MVD显著相关（P〈0.05）,与年龄、性别、肿瘤部位、TNM临床分期及组织学分级无关（P〉0.05）。ET-1和VEGF-C在肿瘤组织中的蛋白表达正相关（r=0.456,P=0.001）。生存分析显示ET-1蛋白阳性表达与生存率无关（P〉0.05）,ET-1＋/VEGF-C＋、VEGF-C蛋白阳性表达与生存率负相关（P〈0.05）,其中ET-1＋/VEGF-C＋阳性表达更具有显著高危死亡率（P=0.000）。Cox回归模型显示ET-1＋/VEGF-C＋可以独立影响预后（P〈0.05）。结论：ET-1和VEGF-C均能促进喉癌淋巴管生成和血管生成。在喉癌组织中ET-1过表达可能通过诱导VEGF-C表达上调促进喉癌淋巴管生成和淋巴结转移。联合检测ET-1及VEGF-C的表达可成为判断喉癌预后的新的生物学指标。     

鼻咽癌p16和CyclinD1表达及其临床意义

[目的]探讨鼻咽癌组织中p16基因缺失和蛋白表达,以及CyclinD1蛋白表达的相关性及其临床意义。[方法]PCR检测151例鼻咽癌标本中p16基因缺失情况,免疫组化SP法检测鼻咽癌和正常鼻咽组织中p16蛋白和CyclinD1蛋白的表达。[结果]鼻咽癌组织中p16第2外显子的缺失率为35.76%（54/151）。p16蛋白在鼻咽癌组织中低表达（P〈0.0001）,但与鼻咽癌患者的性别、年龄、临床分期无相关性（P〉0.05）。CyclinD1蛋白在鼻咽癌组织中高表达（P〈0.0001）,但与鼻咽癌患者的性别、年龄、临床分期均无相关性（P〉0.05）。[结论]鼻咽癌组织中p16第2外显子缺失,p16蛋白低表达而CyclinD1蛋白高表达,两者间呈负相关性（P〈0.0001）。     

FLNA在鼻咽癌发生中的作用及其可能的分子机制

目的：探讨细丝蛋白A（filamin A,FLNA）在鼻咽癌中的表达水平及其过表达对鼻咽癌（nasopharyngeal carcinoma, NPC)细胞生物表型的影响。 方法： 收集2008年1月至2008年12月唐山市人民医院病理科活检取得并经病理证实的新鲜NPC组织标本63例及21例距其癌组织边缘2 cm以上且镜下未见癌浸润的正常鼻咽组织（对照组）,采用免疫组织化学及Western blotting方法检测NPC组织及正常鼻咽组织中FLNA及MMP-9蛋白的表达。以慢病毒转染建立FLNA过量表达的NPC CNE2细胞株,采用RT-PCR及Western blotting检测转染后NPC CNE2细胞株中FLNA的表达变化;MTT法检测FLNA蛋白过量表达对NPC细胞增殖的影响,Transwell实验检测CNE2细胞的侵袭能力。 结果： FLNA蛋白在NPC组织中的阳性表达率明显低于正常鼻咽组织（36.5% vs 66.7%, P <0.05）,其在NPC组织的相对表达量较正常鼻咽组织的相对表达量明显降低\[（0.378±0031） vs （0.835±0.078）, P <0.05\],FLNA蛋白的表达水平与NPC T分期、有无淋巴结转移、临床分期以及组织分级有关（ P <0.05）。FLNA蛋白高表达的CNE2细胞其增殖能力明显减弱、侵袭转移能力明显降低、 MMP-9蛋白表达量明显下调。 结论： NPC组织中FLNA蛋白表达明显降低可能是鼻咽黏膜恶性转变的重要生物学标志,对预测NPC发生、浸润、转移有重要意义。     

血管内皮生长因子C、D在鼻咽癌组织中的表达及其临床意义

背景与目的:血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C)和D(vascular endothelial growth factor-D,VEGF-D)是目前已鉴定出的淋巴管生长因子,有研究表明肿瘤组织中VECF-C或VEGF-D过表达与淋巴转移有关.本研究旨在探讨鼻咽癌组织中VEGF-C和VEGF-D的表达情况及其临床意义.方法:采用免疫组化SP法检测66例鼻咽癌组织中VEGF-C和VEGF-D的表达情况,同时检测血管内皮生长因子受体3(vascular endotheliaI growth factor receptor-3,VEGFR-3)和CD34染色情况并计数微淋巴管密度(lymphatic microvessel density,LMVD)和微血管密度(microvessel density,MVD).结果:VEGF-C高表达率在鼻咽癌组织中(54.5%)较鼻咽非肿瘤组织中(26.3%)高(P＜0.05);鼻咽癌伴区域淋巴结转移或T分期晚者,VEGF-C高表达率增高,单因素及多因素Logistic回归分析均表明区域淋巴结转移与VEGF-C高表达相关(P＜0.05),但VEGF-C高表达与性别、年龄、5年生存率、LMVD、MVD等因素无关(P＞0.05).VEGF-D阳性表达率在鼻咽癌组织中(69.7%)较鼻咽非肿瘤组织中(42.1%)高(P＜0.05);鼻咽癌中VEGF-D阳性表达与性别、年龄、T分期、区域淋巴结转移、LMVD、MVD等因素无关(P＞0.05),但与VEGF-C高表达显著正相关(P＜0.01),VEGF-D阳性表达者5年生存率(50.0%)显著低于VEGF-D不表达者(85.0%)(P＜0.01).结论:鼻咽癌中VEGF-C高表达与区域淋巴结转移密切相关;VEGF-D阳性表达与区域淋巴结转移无关,但与VEGF-C高表达正相关,且与5年生存率密切相关.     

p53和p21WAF1在鼻咽癌rAd-p53瘤内注射前后的表达及其与近期预后的关系

目的探讨重组人p53腺病毒(rAd-p53)瘤内注射前后鼻咽癌(NPC)组织中p53蛋白和p21WAF1蛋白的表达情况,及其与鼻咽癌近期疗效的关系。方法应用免疫组织化学法检测12例鼻咽慢性炎组织和63例确诊中晚期鼻咽癌组织的p53和p21WAF1蛋白表达情况。63例中晚期鼻咽癌随机分为2组:p53治疗组(32例):rAd-p53瘤内注射+同步放化疗;常规治疗组(31例):同步放化疗。分析两组治疗前及放疗至20 Gy时p53和p21WAF1蛋白表达情况及其与预后的关系。结果 NPC组织中p53和p21WAF1蛋白阳性表达率分别为49.21%和46.03%,和鼻咽黏膜慢性炎相比差异有统计学意义(P<0.05)。NPC组织中p53和p21WAF1蛋白表达有相关性(rs=0.556,P=0.000)。放疗前及放疗至20 Gy时,鼻咽癌p53治疗组和p21WAF1蛋白阳性表达率差异有统计学意义(P<0.05);两组p53蛋白和p21WAF1蛋白阳性表达与1年无瘤生存率有关(P<0.05)。结论 rAd-p53瘤内注射后p53和p21WAF1蛋白的阳性表达可能在抑制鼻咽癌复发或转移进程中起着重要作用,并预示较好的预后。     

VEGF-C与鼻咽癌增殖和转移的关系

目的 检测血管内皮生长因子C（VEGF-C）在鼻咽癌（NPC）组织中的表达,探讨其与鼻咽癌细胞增殖和转移的关系。方法NPC患者放疗前的活检组织标本62例,将每例标本均分2份,一份应用VEGF-C多克隆抗体进行SP法免疫组化染色,另一份应用流式细胞术以Ki67抗体检测其增殖状况。放疗后定期随访患者,统计分析其3年生存率及死亡原因。结果62例NPC标本中,VEGF-C表达范围为0～82％,其中阴性（-）17例（27．4％）,弱阳性（＋）13例（21．0％）,中等阳性（＋＋）18例（29．0％）,强阳性（＋＋＋）14例（22．6％）。Ki67表达范围为0-52％,其中低表达（LPI）者40例（64．5％,含15例阴性）,高表达（HPI）者22例（35．5％）。VEGF-C与Ki67表达之间存在明显的正相关（r=0．323,P〈0．05）。3年生存率为66．1％。有淋巴结转移者的VEGF-C表达显著强于无淋巴结转移者（P〈0．01）。8例死于远处转移的患者中,VEGF-C表达均为强阳性;21例无病生存者中,VEGF-C表达为（-）或（＋）者占80．9％。VEGF-C表达与患者预后存在一定的负相关,但差异无统计学意义（r=-0．219,P〉0．05）。结论VEGF-C高表达与鼻咽癌细胞的增殖和转移能力相关,但不是影响患者预后的独立因素,而是一个预测无病生存期长短的指标。     

脑胶质瘤组织p14^ARF、p53和p21^WAF1的表达及其意义

目的：探讨p14^ARF、p53和p21^WAF1蛋白在不同级别脑胶质瘤组织中的表达及其在胶质瘤发生、发展中的生物学意义。方法：应用免疫组化SP法检测Ⅱ级和Ⅳ级胶质瘤组织中p14^ARF、p53和p21^WAF1蛋白的表达,并分析其与胶质瘤组织学分级之间的关系。结果：Ⅱ级和Ⅳ级胶质瘤中,p53蛋白的阳性表达率分别为28．00％（7／25）及60．87％（14／23）（P=0．022）,其阳性表达率随胶质瘤恶性程度的增加而升高,Spearman等级相关分析显示,p53的表达与胶质瘤分级呈正相关（P〈0．05）;p21^WAF1的阳性表达率分别为76．00％（19／25）及39．13％（9／23）（P=0．010）,P14^ARF的阳性表达率分别为76．00％（19／25）及34．78％（8／23）（P=0．004）,二者阳性表达率均随胶质瘤恶性程度的增加而降低,Spearman等级相关分析显示,p21^WAF1、p14^ARF的表达与胶质瘤分级呈负相关（P〈0．05）。结论 胶质瘤组织中,p53呈不同程度的过表达,且随胶质瘤恶性程度的增加而表达水平升高;p21^WAF1、p14^ARF随胶质瘤恶性程度的增加表达水平降低。突变型p53蛋白的过表达以及p21^WAF1、p14^ARF蛋白的低表达,可促进胶质瘤的发生、发展。     

鼻咽癌中ADAM17的表达及其临床意义

摘 要：［目的］ 探讨ADAM17在鼻咽癌(nasopharyngeal carcinoma,NPC)组织中表达与临床预后的关系,及其在鼻咽癌细胞中的生物学功能。［方法］ 免疫组化检测72例鼻咽癌患者和10例正常鼻咽组织标本中ADAM17的表达;Transwell小室实验检测ADAM17对鼻咽癌细胞侵袭和迁移能力的影响。分析ADAM17表达与鼻咽癌患者临床病理特征及预后的关系。［结果］ ADAM17在鼻咽癌组织中的表达水平明显高于正常鼻咽组织（0.204 ± 0.016 vs 0.034 ± 0.006,P<0.01）;ADAM17表达水平与年龄、性别、临床分期和肿瘤大小(T)无关(P>0.05),与淋巴结转移（N）及TNM分期有关（P<0.05）。ADAM17高表达组与低表达组患者的中位总生存期（overall survival,OS）分别为97个月 和109个月(P=0.0087）、中位无进展生存期（progression-free survival,PFS）分别为89个月 和 109个月 （P=0.0229）。COX回归单因素和多因素分析显示ADAM17表达是鼻咽癌OS的独立预后因素（HR=5.974,95%CI：1.307～27.298,P=0.021;HR=4.975,95%CI：1.016～24.368,P=0.048）。Real-time PCR和Western blot实验结果显示与鼻咽永生化上皮细胞NP69相比,ADAM17在 鼻咽癌细胞中表达明显增高,差异有统计学意义;Transwell小室实验结果显示沉默ADAM17后,与si-NC组相比,si-ADAM17组侵袭与迁移的细胞数量明显减少,差异有统计学意义。［结论］ ADAM17在鼻咽癌组织和细胞中异常高表达,并与NPC的分期及不良预后密切相关,沉默ADAM17表达能够有效抑制NPC细胞的侵袭与迁移能力。提示ADAM17在鼻咽癌的侵袭转移进程中具有重要作用,有望成为NPC治疗的新靶点。     

Tobacco, alcohol, diet, occupation, and carcinoma of the esophagus

Information on occupation, smoking, food and beverage consumption, and medical history were compared between 275 incident cases of carcinoma of the esophagus and 275 neighborhood controls who were matched to the cases on age (within 5 years), race, and sex. Tobacco use, mainly cigarette smoking, was a significant risk factor for carcinoma of the esophagus. Ex-smokers of cigarettes showed a reduced risk relative to those who continued to smoke, and current smokers of two or more packs per day displayed a higher risk than those who smoked less. Alcohol consumption was another significant risk factor for carcinoma of the esophagus; there was a highly significant trend with average daily dose of ethanol. Relative to controls, cases also consumed significantly more fried bacon or ham, less fresh fruits and raw vegetables, and were more likely to prefer white than whole grain bread. Finally, there was a significant association between carcinoma of the esophagus and long-term occupational exposure to metal dust; this association was largely confined to the lower one-third section of the esophagus.     

Age,Race, Sex,Stage, and Incidence of Cutaneous Lymphoma

BackgroundThe incidence of the T- and B-cell CLs has been well documented, but information pertaining to racial incidence by age, and by burden of disease (stage) have not been extensively documented.Materials and MethodsThe SEER 2004-2008 public use database was investigated. The relative incidence of CL in different races and age groups was examined. Univariate and multivariate stepwise logistic regression was performed for the likelihood of presenting at a higher stage.ResultsOf 4496 patients diagnosed with CL between 2004 and 2008; 1713 patients were diagnosed with MF, 1518 with non-MF cutaneous T-cell lymphoma, and 1265 patients with cutaneous B-cell lymphoma. For MF, there was a trend for females to be less likely to present with a higher T-stage (T3-T4) than males (odds ratio [OR], 0.73) on multivariate analysis (P = .06). For race, AA had a significantly increased risk of presenting with higher T-stage (T3-T4) MF (OR, 1.72) on multivariate analysis (P = .02), compared with white patients. For white, AA, Asian/Pacific Islander, and Native American/other/unknown, the mean age at diagnosis was 59.2, 51.5, 51.3, and 53.8. These groups presented at a significantly different age than white (P = .0001, 0.0001, and 0.0006).ConclusionNonwhite racial groups present with MF at an earlier age compared with white, and AA have increased risk of presenting with higher T-stage compared with white. These findings have significant implications regarding need for earlier diagnosis and understanding the reasons for racial disparity in age and stage of presentation.     

Fat, fiber, fruits, vegetables, and risk of colorectal adenomas

A case-control study was conducted at the National Naval Medical Center (Maryland, USA) from 1994 to 1996 to investigate the possible association between dietary factors and colorectal adenomas. Cases (n = 239) were subjects diagnosed with adenomas (146 new and 93 recurrent) by sigmoidoscopy or colonoscopy. Those with no evidence of adenomas found by sigmoidoscopy were recruited as controls (n = 228). Dietary variables, assessed by a 100-item food frequency questionnaire, were analyzed by the logistic regression model, which was adjusted for age, gender and total energy intake. Variables of fat intake were further adjusted for red meat intake. An increased risk of 7% [odds ratio (OR): 1.07; 95% confidence interval (95% CI): 0.94-1.22] per 5% energy/day from total fat was observed. Every additional 5% unit of oleic acid intake/day significantly increased the adenoma risk by 115% (OR: 2.15; 95% CI: 1.05-4.39). Red meat fat increased the risk by 20% (OR: 1.20; 95% CI: 0.71-2.04), and white meat fat decreased the risk by 67% (OR: 0.33; 95% CI: 0.19-0.95) for every additional 5% unit of respective intake/day. Risk decreased by 41% (OR: 0.59; 95% CI: 0.41-0.86) for every additional 5% unit of fiber intake/day. Vegetable [OR per 100 g of vegetable intake/day: 0.83, 95% CI: 0.67-1.04] and fruit (OR per 100 g of fruit intake/day: 0.92, 95% CI: 0.82-1.03) intake showed an inverse association, and the results are suggestive of an association with the risk for adenomas. In conclusion, a strong positive association between oleic acid intake and colorectal adenoma risk was observed. This is likely to be an indicator of "unhealthy" food (meat, dairy, margarine, mayonnaise, sweet baked food) consumption in this population. Increased intake of dietary fiber was associated with a moderately decreased risk of adenomas.     

Susceptibility of Ureaplasma urealyticum to Tetracycline,Doxycycline, Erythromycin,Roxithromycin, Clarithromycin,Azithromycin, Levofloxacin and Moxifloxacin

Abstract

The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The miC50 and miC90 of the tested agents after 24 h of incubation were as follows: Tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC₉₀). Overall, moxifloxacin was the most active agent in vitro against U. Urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.     

Occurrence,Efficacy, Metabolism,and Toxicity of Triclosan

Triclosan has broad-spectrum anti-microbial activity against most gram-negative and gram-positive bacteria. It is widely used in personal care products, household items, medical devices, and clinical settings. Due to its extensive use, there is potential for humans in all age groups to receive life-time exposures to triclosan, and, indeed, triclosan has been detected in human tissues and the environment. Data gaps exist regarding the chronic dermal toxicity and carcinogenicity of triclosan, which is needed for the risk assessment of triclosan. The US Food and Drug Administration (FDA) nominated triclosan to the National Toxicology Program (NTP) for toxicological evaluations. Currently, the NTP is conducting several dermal toxicological studies to determine the carcinogenic potential of triclosan, evaluate its endocrine and developmental-reproductive effects, and investigate the potential UV-induced dermal formation of chlorinated phenols and dioxins of triclosan. This paper reviews data on the human exposure, environmental fate, efficacy of anti-microbial activity, absorption, distribution, metabolism and elimination, endocrine disrupting effects, and toxicity of triclosan.     

Susceptibility of Ureaplasma urealyticum to tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin

The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The MIC(50) and MIC(90) of the tested agents after 24 h of incubation were as follows: tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC(90)). Overall, moxifloxacin was the most active agent in vitro against U. urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.     

Histologic features of bladder cancer in Boston,USA, Manchester,UK, and Nagoya,Japan

Histologic characteristics of bladder cancer in Boston, USA, Manchester, UK, and Nagoya, Japan, were evaluated. In each of these areas broadly-based series of cases were assembled during a collaborative case-control study. The present analysis was based on 589 cases in Boston, 484 cases in Manchester, and 241 cases in Nagoya. A single pathologist reviewed a slide of the primary tumor without reference to identifying information or other data. The primary histologic type of nearly all tumors was transitional-cell, and there was little variation in the proportion of transitional-cell tumors among the study areas. Nor was there much variation in the distribution of histologic grade, the proportion of tumors showing submucosal invasion, or the proportion of tumors with a papillary surface. Age at diagnosis was strongly correlated with histologic grade. The proportion of grade III (most malignant) tumors was about twice as high among patients 80 years of age and over as among those aged less than 50. An apparent association between age and submucosal invasion was explained in large part by the relationships of histologic grade to submucosal invasion and to age. Other histologic features had only weak and inconsistent relations with age. None of the features evaluated showed consistent associations with history of cigarettesmoking or with sex.