膀胱癌干细胞关键转录因子Oct4的表达及与肿瘤干细胞的关系

目的检测干细胞关键转录因子Oct4在人膀胱癌组织及细胞系BIU-87中的表达，探讨Oct4的表达在膀胱癌发生发展中的意义及与肿瘤干细胞的关系。方法采用免疫组织化学方法对49例膀胱癌组织病理标本、采用免疫细胞荧光和逆转录-聚合酶链反应（RT—PCR）方法对膀胱癌细胞系BIU-87进行Oct4表达的检测。结果Oct4在膀胱癌中的表达率为81．6％（40／49），Oct4阳性细胞率约为0．6％，Oct4表达的阳性细胞率及强度与膀胱癌的分级、复发和转移无明显相关性（P〉0．05）。在BIU-87细胞中存在少量的Oct4阳性细胞，RT-PCR证实存在Oct4的弱表达。结论膀胱癌中有少量细胞表达全能干细胞标志物Oct4，这些细胞很可能是膀胱癌干细胞，这将为其最终分离和鉴定人膀胱癌干细胞提供重要的基础。     

血栓调节蛋白在肾脏肿瘤组织中的表达及临床意义

目的研究血栓调节蛋白（TM）在肾盂移行细胞癌及肾细胞癌中的表达及临床意义。方法选择40例不同分期、不同分级的肾盂移行细胞癌及20例不同分期、不同分级的肾细胞痛标本，应用免疫组织化学SP法研究TM的表达。结果40例肾盂移行细胞癌，TM表达者37例（92．5％），20例肾细胞癌，TM表达1例（5％），其两组表达率明显不同（P〈0．01）。肾盂移行细胞癌组织TM表达阳性细胞百分数随病理分级、临床分期的上升而下降（P〈0．01或P〈0．05）。另外TM表达阴性者再发膀胱癌发生率为66．7％，TM表达细胞百分数小于41．7％的患者中再发膀胱癌发生率为62．5％，TM表达细胞百分数大于41．7％的患者中再发膀胱癌发生率为3．4％，前两者与后者相比，其再发膀胱癌发生率明显升高（P〈0．01）。结论TM表达量与肾盂移行细胞癌的恶性程度、病程情况等生物学行为有关。TM表达阴性及TM表达阳性细胞百分数小于41．7％的肾盂移行细胞癌再发膀胱癌可能性大，应对此类肾盂移行细胞癌患者术后按膀胱肿瘤对待。TM可以作为一种瘤标来鉴别诊断肾盂移行细胞癌与肾细胞癌。     

Caveolin-1和E-cadherin在肾细表达及其意义胞癌中的

目的：探讨Caveolin-1、E—cadherin在肾细胞癌中的表达及其临床意义。方法：采用免疫组织化学EnVision法检测41例肾细胞癌切除标本中Caveolin-1和E—cadherin的表达，并分析表达情况与肿瘤的生物学行为的关系。结果：Caveolin-1在肾细胞癌中的表达阳性率为41．5％，与肿瘤分期、Fuhrman分级及患者年龄呈正相关（P〈0．05）；E-cadherin表达阳性率为24．4％，低于癌旁肾组织（50％），E—cadherin表达与肿瘤细胞核分级相关（P〈0.05），与其他临床病理参数之间无相关性。Caveolin-1和E-cadherin两者之间表达无相关性。结论：Caveolin-1过表达及E-cadherin的异常表达，可能在肾细胞癌的生长、分化中发挥重要作用。     

肾细胞癌病理亚型相关的二次原发肿瘤

作者评价肾细胞癌组织病理亚型——透明细胞癌、乳头状癌和嫌色细胞癌罹患二次肿瘤的风险。回顾性分析1970年至2000年因散发肾细胞癌行肾切除的2722例患者的病例资料，所有病理标本都由一位泌尿外科病理医师进行分型，二次原发肿瘤与肾细胞癌病理亚型的关系通过X^2检验和Fisher精确检验评价。结果：所有患者中，透明细胞癌2188例（80．4％），乳头状癌378例（13．9％），嫌色细胞癌128例（4．7％）。乳头状肾细胞癌患者比透明细胞癌患者更容易患结肠癌（P=0．041）、前列腺癌（P=0．003）和其他肿瘤（P＜0．001）。     

CD40分子在肾癌组织中的表达研究

目的探讨肾癌组织中CD40分子的表达与癌发生浸润转移的关系。方法用免疫组织化学二步法（Envision法）对甲醛固定石蜡包埋的肾细胞癌组织（32例）和癌旁组织（10例）中CD40的表达情况进行研究，并分析CD40分子表达水平与肾癌临床分期、病理分级和发生淋巴结转移的相关性。结果CD40在肾细胞癌组织中表达的阳性率为87．5％，与肾癌癌旁组织组相比，具有显著性差异（P〈0．01）；CD40的阳性过度表达与肿瘤临床分期、病理组织学分级和淋巴结转移显著相关（P〈0．05）。结论CD40分子在肾癌中的异常表达可为肾癌的诊断、治疗及指导预后提供实验依据，并为进一步研究肾癌的生物学，尤其是为抑制Fas和TNFR介导的细胞凋亡与基因治疗肾细胞癌打下基础。     

fascin及Galectin-3在肾细胞癌中的表达及意义

目的：观察fascin在肾细胞癌中的表达情况,并探讨其表达与肿瘤生物学行为及临床、病理指标的关系。方法：用免疫组织化学方法检测114例肾细胞癌组织及30例正常。肾组织中fascin和Galectin3的表达。分析fascin表达与不同临床病理指标及Galectin3表达之间的关系。结果：fascin及Galectin-3在正常肾组织均无表达,114例肾细胞癌标本中fascin有80例呈阳性表达,Galectin-3有68例呈阳性表达,差异有统计学意义（P〈0．01）。在肾细胞癌标本中fascin表达与肿瘤浸润程度、淋巴转移、临床分期、病理类型具有相关性（P〈0．05）,与年龄、性别、肿瘤的侧别、肿瘤的部位无相关性（P〉0．05）．fascin与Galectin-3在肾细胞癌中表达具有明显的正相关性（P〈0．01）。结论：fascin与Galectin-3在肾细胞癌中表达上调且和肿瘤的进展相关。fascin、Galectin-3表达和l临床分期结合能够更好地判断‘肾细胞癌的预后,且其有可能成为肾细胞癌治疗的一个新靶点。     

肾细胞癌VHL基因改变与VEGF表达的关系及意义

目的：探讨肾细胞癌VHL基因异常与血管内皮生长因子（VEGF）表达的关系及意义。方法：应用聚合酶链反应（PCR）加单链构象多态性分析（SSCP）、多聚合酶链反应（Multiplex-PCR)及免疫组织化学方法检测42例肾细胞癌、18例远离肿瘤的正常肾脏及10例正常肾脏组织中VHL基因突变、异常甲基化及VEGF的表达。结果：肾癌组织中VHL基因改变（61．9％）与正常肾脏组织（3．6％）比较差别有显著性意义（P＜0．005）,VHL基因失活与肾癌组织类型及临床分期相关,与病理分级无关。VEGF在肾癌组织（64．3％）与正常肾组织（21．4％）中的表达差别有显著性意义（P＜0．005）,肾癌组织中VEGF表达与组织类型无关,与病理分级及临床分期相关,随病理分级及临床分期的升高而增高。VHL基因改变与VEGF表达间存在显著的相关性（P＜0．05）。结论：VHL基因在肾细胞癌中具有高频突变率,可负向调节VEGF的表达。     

肾癌患者外周血中survivin mRNA的表达

目的探讨肾透明细胞癌患者外周血中survivin mRNA的表达及其临床意义。方法用RT-PCR方法检测30例肾透明细胞癌患者、10例正常健康人外周血中survivin mRNA的表达。结果30例肾透明细胞癌患者中有23例外周血中survivin mRNA表达阳性，阳性率为76．7％，与正常健康人（0％）相比差异有统计学意义（P〈0．001）；survivin mRNA的表达与临床分期密切相关（P〈0．01）；随肿瘤组织分化程度的降低，survivin阳性率有增加的趋势，但差异无统计学意义（P〉0．05）。结论肾透明细胞癌患者外周血中survivin mRNA可作为肾透明细胞癌微转移的一个监测指标。     

Fascin蛋白在肾细胞癌中的表达及临床意义

目的观察Fascin蛋白在肾细胞癌中的表达情况,并探讨其表达与肿瘤生物学行为及临床病理指标的关系。方法用免疫组织化学方法检测109例肾细胞癌组织、20例肾脏良性肿瘤和20例正常肾脏组织中Fascin蛋白和Ki-67的表达,分析Fascin蛋白表达与不同临床病理指标及Ki-67表达之间的关系。结果109例肾细胞癌中有58例（53．2％）Fascin蛋白呈阳性表达,20例肾脏良性肿瘤和20例正常肾脏组织中的阳性表达例数分别为2例（10．0%）和0例（0%）,肾细胞癌中Fascin蛋白表达与肾脏良性肿瘤和正常肾脏组织中Fascin蛋白表达比较差异均有统计学意义（均P〈0．01）。肾细胞癌组织中Fascin蛋白表达与肿瘤组织学分级、临床分期、淋巴结转移以及Ki-67表达均呈正相关（均P〈0．01）;与肿瘤组织学分类无相关性（P〉0．05）。结论Fascin蛋白在肾细胞癌中表达上调且和肿瘤的恶性程度及侵袭行为有关。Fascin蛋白表达与病理分级和临床分期结合能够更好地判断肾细胞癌的预后,且其有可能成为肾细胞癌治疗的一个新靶点。     

不同类型膀胱癌组织中环氧化酶-2的表达及意义

目的探时环氧化酶-2（COX-2）在不同类型膀胱癌组织中的表达及临床意义。方法应用免疫组化染色方法检测52例膀胱移行细胞癌组织（其中T，18例、T2 14例、T3 14例、T4 6例，G1 13例、G2 25例、G3 14例，肿瘤单发37例、多发15例）、20例膀胱腺癌组织、10例膀胱鳞状细胞癌组织及17例正常膀胱黏膜组织中COX-2蛋白表达情况，根据染色阳性细胞所占比例，分为（-）、（＋）、（＋＋）、（＋＋＋）4个等级，用等级资料x^2检验进行统计学分析。结果82例肿瘤组织COX-2蛋白表达率（82．9％，68／82）高于正常黏膜（23．5％，4／17）（P〈0．05），不同类型肿瘤COX-2蛋白表达率也有差别，鳞状细胞癌最强（100％，10／10），腺癌次之（90．0％，18／20），移行细胞癌相对较弱（76．9％，40／52）（P〈0．05）；在52例移行细胞癌标夺中，COX-2表达率与肿瘤分级、分期相关（P〈0．05）。结论COX-2在不同类型膀胱癌组织中呈岛表达，在鳞状细胞癌表达最强，可能成为膀胱癌化学预防的一个靶点。     

Fas和FasL蛋白在肾癌组织中的表达及意义

目的　探讨凋亡相关基因产物Fas和FasL蛋白在肾癌发生中的作用以及与转移、预后的关系。方法　采用免疫组织化学方法对46例肾癌组织和15例正常肾组织Fas和FasL蛋白的表达进行检测。结果　肾癌组织Fas表达率为18.14%,低于正常肾组织（46.15%,P<0.05）,随肾癌分级的增加,表达强度下降。肾癌组织FasL蛋白表达率为70.26%,高于正常肾组织（10.32%,P<0.05）,随肾癌分级的增加,表达强度增高。正常肾组织Fas与FasL的表达有相关性（r=0.689,P<0.05）,肾癌组织无相关性（r=0.143,P>0.05）,有淋巴结转移组FasL(89.42%)与无淋巴结转移组(60.39%)比较,差别有显著性意义(P<0.01)。生存率>5年组Fas(25.39%)和FasL(61.26%)与生存率<5年组Fas(15.24%)和FasL(85.35%)的差别均有显著性意义(P均<0.05)。结论　Fas和FasL蛋白相互作用失衡在肾癌的发生、发展中起重要作用,表达情况与肾癌病理分级及转移、预后有一定关系。     

肾细胞癌组织中DLK1蛋白表达及与临床病理学特征的相关性研究

目的 探讨不同组织类型的肾细胞癌组织中DLK1蛋白表达与肾癌临床病理特征及转移的关系.方法 采用免疫组织化学方法,检测94例肾原发透明细胞癌、76例乳头状肾细胞癌、45例嫌色细胞癌、71例透明细胞癌远处转移灶、24例透明细胞癌淋巴结转移灶及18例正常肾组织标本中DLK1蛋白表达情况,分析其与临床病理特征及转移的相关性.结果 正常肾组织近端及远端肾小管中DLK1蛋白表达均为阳性,透明细胞癌、乳头状肾细胞癌及嫌色细胞癌组织低表达率分别为33.0%(31/94)、27.6%(21/76)及33.3%(15/45),与正常肾组织相比,差异有统计学意义(P＜0.05),3种类型肾癌组织之间DLK1蛋白表达差异无统计学意义(P＞0.05).DLK1蛋白表达水平与透明细胞癌患者性别(男60例,女34例)、年龄(≥55岁50例,＜55岁44例)、病理分期(Ⅰ期41例,Ⅱ期9例,Ⅲ期21例,Ⅳ期23例)及淋巴结转移状态(无转移76例,有转移18例)等无明显相关性(P＞0.05).透明细胞癌原发灶、淋巴结转移灶、远处转移灶肿瘤组织中DLK1蛋白表达差异无统计学意义(P＞0.05).结论 不同类型的肾细胞癌组织中DLK1蛋白表达降低.DLK1蛋白低表达与透明细胞癌的临床病理特征及肿瘤转移无关.

Abstract：

Objective To identify the expression of DLK1 protein in different types of renal cell carcinomas and its correlations with pathological characteristics and metastasis. Methods Immunohistochemistry analysis was performed to evaluate the expression of DLK1 protein in 94 cases of primary clear cell renal cell carcinoma, 76 cases of papillary renal cell carcinoma, 45 cases of chromophobe renal cell carcinoma, 71 cases of distal metastatic and 24 cases of lymph node metastatic clear cell renal cell carcinoma, as well as 18 cases of normal renal tissue. The correlations of DLK1 protein expression with pathological characteristics were analyzed. Results DLK1 protein was expressed in proximal and distal renal tubular epithelial cells in all the normal renal cases. In contrast, DLK1 protein expression was lower in different types of renal cell carcinoma. The low or negative expression of DLK1 protein in clear cell renal cell carcinoma, papillary renal cell carcinoma and chromophobe renal cell carcinoma was 33.0% (31/94), 27.6% (21/76) and 33.3% (15/45), respectively. Compared to normal renal tissue, DLK1 protein expression was significantly down-regulated in renal cell carcinomas (P＞0.05), whereas there was no significant difference on DLK1 protein expressions among the different types (P＞0.05) of renal cell carcinomas. DLK1 protein expression was not correlated with sex (60 male and 34 female cases), age (≥55, 50 cases and 55, 44 cases), grade (41 cases in grade I, 9 cases in grade II, 21 cases in grade III and 23 cases in grade Ⅳ respectively) and lymph node metastasis (76 cases with and 18 cases without lymph node metastasis) in clear cell renal cell carcinoma (P＞0.05). There was also no significant difference among primary, lymph node and distal metastatic lesions of clear cell carcinoma (P＞0.05). Conclusions DLK1 protein expression is commonly down-regulated in different types of renal cell carcinomas. Down-regulation of DLK1 protein expression is not associated with pathological characteristics and metastasis in clear cell renal cell carcinoma.     

Fas mRNA在泌尿系肿瘤组织中的表达

目的 了解Ｆａｓ ｍＲＮＡ在泌尿系肿瘤组织中的表达情况。方法 采用逆转录ＰＣＲ（ＲＴ－ＰＣＲ）法检测３７例泌尿系恶性肿瘤组织中Ｆａｓ ｍＲＮＡ的表达，其中肾癌２１例，膀胱癌１１例、肾盂癌４例，前列腺肉瘤１例；原位杂交法检测３４例肾癌和１９例癌旁正常肾组织中Ｆａｓ ｍＲＮＡ的表达。结果 ３７例肿瘤组织中检出Ｆａｓ ｍＲＮＡ阳性表达共２０例，阳性率为５４％，阳性表达组织中未发现有缺失突变的存在。其中肾     

Mechanisms and modulation of multidrug resistance in primary human renal cell carcinoma

Human renal cell carcinomas show a high degree of intrinsic multidrug resistance. In experimental cell lines, the membrane bound P-170 glycoprotein and the glutathione redox cycle seem to contribute to this phenomenon. P-170 may be inactivated by calcium antagonists; the glutathione redox cycle by buthionine sulfoximine. We studied the resistance patterns of 35 human renal cell carcinomas against vinblastine, doxorubicin and carboplatinum in a tetrazolium-based microculture assay. Concomitantly, P-170 expression was traced immunohistochemically using moab C219 and the glutathione content was determined enzymatically. Reversal of multidrug resistance was examined by applying the R-stereoisomer of verapamil and/or by addition of buthionine sulfoximine. A high degree of chemoresistance was seen in 27 tumors against vinblastine, in 30 tumors against doxorubicin and in 31 tumors against carboplatinum. Chemoresponse was found in eight, five or four cases respectively. P-170 was detected in 70% of highly vinblastine resistant and in 63% of highly doxorubicin resistant tumors, but in none of the less resistant cases. Resistance against carboplatinum and doxorubicin was significantly associated with elevated glutathione levels as compared to less resistant renal cell carcinomas. R-verapamil lead to a strong reversal of vinblastine resistance and to a distinct circumvention of doxorubicin resistance, but revealed no effect in carboplatinum resistance. Buthionine sulfoximine overcame carboplatinum resistance and modified doxorubicin resistance, but had no influence on vinblastine resistance. The combined application of R-verapamil and buthionine sulfoximine reversed doxorubicin resistance but did not act synergistically in vinblastine or carboplatinum resistance. Both mechanisms, P-170 and glutathione, occurred independently of each other and may well explain multidrug resistance of human renal cell carcinomas.     

P63蛋白在肾盂移行上皮细胞癌和肾细胞癌中的表达及临床意义

目的探讨P63基因在肾盂移行细胞癌（renal transitional cell carcinoma，RTCC）和肾细胞癌（renal cell carcinoma，RCC）组织中的表达及其意义。方法采用免疫组织化学SP法检测40例RTCC、50例RCC、10例正常肾组织中P63的表达，并分析P63表达与RTCC及RCC病理分级、临床分期、病理类型间的关系。结果正常。肾组织、RTCC、RCC中P63的阳性表达率分别为30％（3／10）、95％（38／40）、0％（0／50），组间差异有统计学意义（P〈0．01）；RTCC组中G1级与G2级P63的强阳性、中度阳性表达率显著高于G3级（P〈0．05）；Ta-T1期以P63强阳性为主（66．7％），随RTCC浸润程度的增加，P63染色强度逐渐减弱；T2期P63强阳性表达率为42．9％，T3-T4期降至0；RCC组中，所有肿瘤无论组织类型、级别、分期，P63表达均呈阴性。结论P63在RTCC中高表达，与RTCC病理分级、临床分期密切相关；P63可能参与RTCC的发生、发展，是评估RTCC预后的潜在因素之一；P63在RCC中不表达，可作为将RTCC从RCC中鉴别出来的有用指标之一。     

Renal sinus involvement in renal cell carcinomas

The renal sinus is the fatty compartment located within the confines of the kidney not delineated from the renal cortex by a fibrous capsule. Because it contains numerous veins and lymphatics, invasion into this compartment may permit dissemination of a tumor otherwise regarded as renal-limited. Thirty-one consecutive renal carcinomas were studied: 22 clear cell renal cell carcinomas (3 multilocular cystic renal cell carcinomas), 4 chromophobe renal carcinomas, and 5 papillary renal carcinomas. The entire interface between the neoplasm and the sinus was embedded. Seventeen carcinomas did not invade the renal sinus and 16 were pT1 or pT2 tumors. Fourteen carcinomas, 13 clear cell renal cell carcinoma and one chromophobe renal carcinoma, invaded the renal sinus fat, and 9 of 14 invaded the lumen of renal sinus veins (all clear cell renal carcinomas). Although 14 of 22 clear cell renal carcinomas appeared to be renal limited pT1 and pT2 cancers, 6 of 14 carcinomas invaded sinus fat and 4 invaded into the lumen of renal sinus veins. Compared with the nine sinus-negative clear cell renal cell carcinomas, the 13 sinus-positive cancers were larger, exhibited more frequent renal capsule and renal vein involvement, and had higher nuclear grades. Renal sinus invasion was most common in clear cell renal cell carcinomas but was uncommon (one in 12) in 3 more indolent renal cell carcinomas: multilocular cystic renal cell carcinoma, chromophobe renal carcinoma, and papillary renal carcinoma. The follow-up period was short (1-17 months), but metastases developed in four of 31 cases. In three cases with metastases, carcinoma had involved the lumen of sinus veins but not the main renal vein, although two of three had also invaded through the renal capsule. This study shows that in carcinomas which appear to be renal limited (pT1/pT2), seven of 23 (30.4%) had invaded sinus fat and four of 23 (17.4%) had invaded sinus veins. We conclude that renal sinus invasion, especially sinus vein invasion, could identify a patient at risk for metastases even in a putative renal limited tumor, and suggest that all cases be examined for this feature. Renal sinus invasion merits further investigation to establish its prognostic importance and possible incorporation into future revisions of the TNM staging system for renal cell carcinomas.     

Inhibin alpha distinguishes hemangioblastoma from clear cell renal cell carcinoma

Inhibin alpha subunit (inhibin A) expression in hemangioblastomas has not been previously reported in the literature. We analyzed the expression of inhibin A in 25 hemangioblastomas from 22 patients. Eleven cases were from 8 patients with von Hippel-Lindau disease, and these tumors were multicentric and/or recurrent. The remaining 14 cases from 14 patients were sporadic. The male-to-female ratio was 8:3, and the age at presentation ranged from 19 to 78 years (mean 35 years; median 45 years). Eighteen tumors were located in the cerebellum/posterior fossa, 1 in the medulla, 1 in the occipital lobe, and 5 in the spinal cord. Four metastatic renal cell carcinomas in brain, 10 renal cell carcinomas from 8 patients with von Hippel-Lindau disease, and 5 sporadic clear cell renal cell carcinomas were also included. Two patients with von Hippel-Lindau disease had both renal cell carcinoma and hemangioblastoma. The stromal cells of all 25 cases of hemangioblastoma expressed inhibin A. Strong, moderate, and weak cytoplasmic immunoreactivity was noted in 17, 5, and 3 cases, respectively. In contrast, none of the 19 renal cell carcinomas, primary as well as metastatic, expressed inhibin A. There was no difference in the inhibin A staining pattern between the sporadic hemangioblastoma and those associated with VHL. These findings demonstrate inhibin A to be a useful marker in distinguishing hemangioblastoma from metastatic clear cell renal cell carcinoma. While the diagnostic importance is evident, the pathophysiology of inhibin A expression by the stromal cells of hemangioblastoma remains unknown and further investigation is required.     

Expression of vimentin in surgically resected adenocarcinomas and large cell carcinomas of lung

The expression of vimentin in pulmonary carcinomas was studied in 285 cases of surgically resected lung cancer from our hospital files. Formalin fixed, paraffin-embedded sections were studied by immunoreactive staining techniques using two monoclonal antibodies against vimentin. Cases demonstrating vimentin positivity by the avidin-biotin-peroxidase method included 11 of 129 adenocarcinomas studied (8.5%), and 15 of 61 large cell carcinomas studied (24.6%). Vimentin expression was not seen in any of the 51 squamous cell carcinomas or 35 small cell carcinomas in our series. The positive cases of adenocarcinoma were in moderately and poorly differentiated cancers. Four of the eight giant cell carcinomas (50%) demonstrated vimentin expression. All cases that exhibited vimentin positivity were studied for cytokeratin expression. Coexpression of vimentin and cytokeratin was demonstrated not only within the same tumor but also within the same cells in some cases stained by double antibody technique, including both adenocarcinomas and large cell carcinomas. Similar immunoreactive methods were also applied to sections from human lung cancer transplants grown in the nude mouse. Of 28 tumors studied, four of 11 adenocarcinomas (36%) and all 4 large cell carcinomas demonstrated coexpression of vimentin and cytokeratin, while none of the five squamous cell carcinomas or eight small cell carcinomas expressed vimentin.     

前列腺潜伏癌及偶发癌的病理学特征研究

目的研究前列腺潜伏癌及偶发癌肿瘤形态学、增殖状态及基质金属蛋白酶-2 (MMP-2)、MMP-9表达与临床癌的差异。方法收集前列腺潜伏癌组织标本24例、偶发癌组织标本5例、临床癌组织标本38例,常规染色观察其组织学特征,免疫组织化学SP法检测Ki-67、细胞增殖核抗原(PCNA)、MMP-2、MMP-9的表达。结果潜伏癌及偶发癌组Gleason评分较低,临床癌组的评分较高。潜伏癌及偶发癌组中有核仁者为62.1%(18/29),明显低于临床癌组的94.7%(36/38)(P<0.05)。潜伏癌及偶发癌组Ki-67及PCNA的表达率为0及13.8%(4/29),均明显低于临床癌组的54.8%(17/31)及91.9%(34/37)(P<0.05)。临床癌组中MMP-2、MMP-9的阳性表达率分别为73.0%(27/37)、68.4%(26/38),明显高于潜伏癌及偶发癌组的23.8%(5/21)、28.6%(4/14),差异有统计学意义(P<0.05)。结论前列腺潜伏癌及偶发癌在组织结构、核仁特点、增殖状态及MMP-2、MMP-9表达均与临床癌有所不同。前列腺潜伏癌及偶发癌与临床癌可能是有不同分化程度、不同增殖活性及不同侵袭性的两类病变。     

Expression of alpha-methylacyl-CoA racemase in papillary renal cell carcinoma

Alpha-methylacyl-CoA racemase (AMACR) was first discovered by using cDNA microarray technology as a molecular marker for prostate cancer. Our recent microarray analysis of renal cell carcinomas showed a significant increase of AMACR mRNA levels in papillary renal cell carcinomas, but not in other subtypes. To investigate the value of this marker in pathologic diagnosis, we analyzed AMACR mRNA levels in cDNA microarrays from 70 kidney tumors. Furthermore, we evaluated the AMACR expression in 165 kidney tumors on tissue microarrays and 51 papillary carcinomas of other organs by immunohistochemistry. AMACR mRNA was significantly overexpressed in 7 of 8 papillary renal cell carcinomas with an average of 5.2-fold increase, and only in 2 of 62 nonpapillary kidney tumors. Immunohistochemistry demonstrated strong AMACR positivity in all cases of papillary renal cell carcinomas (41 of 41, 100%), including 6 metastatic papillary renal cell carcinomas, but only focal or weak reactivity in the minority (18 of 124, 15%) of other renal tumors including 13 of 52 clear cell renal cell carcinomas, 3 of 20 oncocytomas, and 2 of 17 urothelial carcinomas. All chromophobe (0 of 18) and sarcomatoid components of renal cell carcinomas (0 of 15) were negative for AMACR. Weak or focal AMACR immunoreactivity was detected in only 4 of 51 (8%) papillary carcinomas arising in other organs (2 of 14 thyroid, 2 of 13 lung, 0 of 6 breast, 0 of 6 endometrium, 0 of 6 ovary, and 0 of 6 pancreas). Using a combination of cDNA microarrays, tissue microarrays, and immunohistochemistry, we identified AMACR as a marker for papillary renal cell carcinoma, which could be valuable in subclassification of renal cell carcinomas and in the differential diagnosis of a metastatic papillary carcinoma.