HMGB1和MMP2在肾透明细胞癌中的表达及意义

目的 研究高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)和基质金属蛋白酶2(matrix metalloproteinase-2,MMP2)在肾透明细胞癌(renal clear cell carcinoma,RCCC)中的表达及临床意义.方法 收集58例RCCC、30例癌旁非癌肾组织、18例正常肾组织,采用免疫组织化学二步法检测HMGB1和MMP2的表达,并分析它们与临床病理参数之间的关系.58例RCCC中,组织学分级为高分化24例、中分化16例、低分化18例;临床分期为Ⅰ期13例、Ⅱ期15例、Ⅲ期21例、Ⅳ期9例.结果 HMGB1在正常肾组织、癌旁组织、RCCC中的阳性表达率分别为22.2%、36.6%、82.7%,呈现逐渐升高的趋势(P＜0.05);在RCCC中,HMGB1蛋白阳性表达率在临床分期Ⅲ期和Ⅳ期高于Ⅰ期和Ⅱ期,有淋巴结转移组高于无淋巴结转移组,肿瘤直径≥5 cm组高于肿瘤直径＜5 cm组,肿瘤有坏死组高于无坏死组,HMGB1表达与年龄、性别、分化程度、肿瘤所在部位均无关(P＞0.05).MMP2在正常肾组织、癌旁组织、RCCC中的阳性表达率分别为16.6%、33.3%、79.3%,呈现逐渐升高的趋势(P＜0.05);在RCCC中,MMP2蛋白阳性表达率在临床分期Ⅲ期和Ⅳ期高于Ⅰ期和Ⅱ期,低分化组高于中、高分化组,有淋巴结转移组高于无淋巴结转移组,MMP2表达与年龄、性别、肿瘤所在部位、大小、是否坏死均无关(P＞0.05).结论 HMGB1和MMP2蛋白的高表达参与了RCCC的发生、发展,可以作为判断RCCC预后的分子指标.     

肾透明细胞癌中转录因子Sp1和Survivin的联合表达及临床意义

目的研究Sp1和Survivin在肾透明细胞癌（RCCC）组织中的表达及临床意义。方法用免疫组织化学PV-6000法,检测Sp1和Survivin蛋白在59例RCCC和11例正常肾组织中的阳性表达,并分析其相关性。结果Sp1和Survivin在正常肾组织中低表达,在肾癌组织中高表达,二者在RCCC的阳性表达率分别为71．2％（42／59）和66．1％（39／59）。Sp1阳性表达率与RC—CC组织学分级、临床分期关系密切,且与Survivin阳性表达呈正相关（r=0．572,P〈0．05）。结论Sp1和Survivin在RCCC的发生和恶性进展中均发挥重要作用,二者的联合检测对于判断RCCC的预后有较大价值。     

基质金属蛋白酶-9及其抑制因子在肾细胞癌组织中的表达和意义

目的　探讨基质金属蛋白酶 9(MMP 9)和金属蛋白酶组织抑制因子 1(TIMP 1)在肾细胞癌中的表达及其与临床病理参数之间的关系。方法　采用免疫组织化学链霉菌抗生物素蛋白过氧化酶 (SP)法检测 5 5例肾细胞癌中MMP 9和TIMP 1的表达情况。结果　MMP 9、TIMP 1蛋白在肾细胞癌和正常肾组织中的阳性表达率各为 63 .63 %和 10 .0 0 % (P <0 .0 5 ) ;60 .0 0 %和10 .0 0 % (P <0 .0 5 )。在肾癌中 ,MMP 9蛋白表达与肿瘤Robson分期、肾包膜侵袭和淋巴结转移密切相关 (P <0 .0 5 ) ,而与组织学类型无关 (P >0 .0 5 ) ;TIMP 1蛋白表达与肾细胞癌的临床病理参数无关 (P >0 .0 5 )。结论　MMP 9蛋白高表达参与了肾癌的发展 ,MMP 9和TIMP 1的平衡失调可能在肾癌的侵袭转移中发挥重要作用。     

肾癌PD-ECGF的表达及其临床意义

目的：探讨血小板衍化内皮生长因子（PD-ECGF）在肾透明细胞癌（RCCC）的表达及临床意义。方法：应用免疫组织化学技术检测43例RCCC标本中PD-ECGF的表达,并分析其与RCCC的临床分期、病理分级及浸润、转移的关系。结果：43例RCCC中PD-ECGF的阳性表达率为67．4％（29／43）,对照组12例正常肾组织未能发现阳性表达。PD-ECGF的表达与RCCC临床分期显著相关,T3～4显著高于T1～2期（P〈0．01）,不同病理分级的表达差别无显著性意义。结论：PD-ECGF在RCCC的发生发展中起重要作用。与RCCC的浸润、转移相关。     

存活素、bcl-2在肾透明细胞癌中的表达及其临床意义

目的探讨存活素、bcl-2在肾透明细胞癌（RCCC）中的表达及意义。方法应用免疫组化技术检测存活素、bcl-2在82例RCCC和20例正常肾组织的表达。RCCC患者年龄26～78岁，肿瘤大小0．8～7．2cm。结果存活素在RCCC的阳性表达率为78％（64／82），高于正常肾组织的0％（0／20），P〈0．01，存活素表达与临床分期有关，但与性别、年龄、肿瘤大小及分化程度无明显相关；bcl-2在RCCC的阳性表达率为70％（57／82），高于正常肾组织的35％（7／20），P〈0．01，bcl-2表达与肿瘤分化程度、临床分期无明显相关。RCCC组织中存活素表达与bcl-2表达无相关性。结论存活素、bcl-2异常表达与RCCC的发生发展密切相关，存活素高表达预示不良预后。存活素可能成为RCCC的一个重要诊断指标和治疗靶点。     

MMP-2和TIMP-2蛋白在乳腺癌组织中的表达及其与肿瘤转移的关系

为探讨乳腺肿瘤组织中细胞外基质金属蛋白酶 -2 (MMP 2 )和组织基质金属蛋白酶抑制剂 -2 (TIMP 2 )的表达情况 ,研究及其与乳腺肿瘤发生、发展中的生物学意义并观察其与乳腺癌浸润及转移的相关性 ,作者采用免疫组化方法检测 5 8例乳腺浸润性导管癌及 2 0例乳腺纤维腺瘤的组织标本中MMP 2和TIMP 2的表达情况并进行对比观察。结果示 5 8例乳腺癌和 2 0例乳腺纤维腺瘤的组织中MMP 2的表达分别为 43 .1%(2 5 / 5 8)和 10 %(2 / 2 0 ) ;TIMP 2的表达分别为 5 5 .17%(3 2 / 5 8)和 90 %(18/ 2 0 )。MMP 2的高表达与肿瘤的病理分级、淋巴结转移呈正相关 ,TIMP 2阳性表达与肿瘤的病理分级、淋巴结转移呈负相关。提示MMP 2和TIMP 2的表达与乳腺癌的浸润和淋巴结转移密切相关 ,MMP 2阳性表达率上升和 /或TIMP 2阳性表达率下降 ,表示乳腺癌浸润及转移能力增强 ,联合检测两指标有助于乳腺癌浸润转移和预后的判断。     

膀胱癌中MMP-2、TIMP-2的表达及其与浅表性肿瘤复发的关系

目的：研究基质金属蛋白酶－2（MMP－2）和金属蛋白酶组织抑制因子－2（TIMP－2）在膀胱癌中的表达以及它们与肿瘤临床病理因素和复发的关系。方法：用免疫组织化学SP法检测46例膀胱移行细胞癌标本中MMP－2、TIMP－2的表达，并将它们与肿瘤临床和病理参数相比较。结果：在46例膀胱癌中，MMP－2、TIMP－2的阳性率分别为47.8%和58.7%，TIMP－2在间质中的表达率为47.8%。MMP－2表达率随着肿瘤理分级、临床分期的升高而增加，而TIMP－2表达率则呈下降趋势，但在浅表性膀胱癌（Ta-T1）中，TIMP－2的表达与MMP－2相似，随着肿瘤分期分级的升高而增加，TIMP－2间质表达阳性组中浅表性膀胱癌的2年复发率显著高于表达阴性组。结论：MMP－2和TIMP－2的相互作用对于膀胱癌的侵袭发展发挥了重要作用。TIMP－2在间质中表达可作为判断浅表性膀胱癌复发的预后指标。     

低氧诱导因子2和血管内皮生长因子在膀胱癌中的表达及意义

目的　探讨低氧诱导因子 2 (EPAS1/HIF 2α)和血管内皮生长因子 (VEGF)在膀胱移行细胞癌中的表达意义。　方法　应用免疫组织化学技术检测 6 0例膀胱移行细胞癌 [Ⅰ级 2 8例 ,Ⅱ级 12例 ,Ⅲ级 2 0例 ;浅表性膀胱癌 (Tis～T1) 2 9例 ,浸润性 (T2 ～T4) 31例 ]和 8例正常膀胱组织中EPAS1/HIF 2α和VEGF的表达情况 ,χ2 检验分析其表达与膀胱癌分级和分期间的关系。　结果　EPAS1/HIF 2α和VEGF在正常膀胱组织中不表达 ,而在膀胱癌组织表达较强。 6 0例膀胱癌标本中EPAS1/HIF 2α阳性表达 34例 ,阴性 2 6例。病理分级Ⅰ级标本阳性表达 4例 (14 .3% ) ,Ⅱ级 11例 (91.7% ) ,Ⅲ级 19例(95 .0 % )。浅表性癌中阳性 5例 (17.2 % ) ,浸润性癌中阳性 2 9例 (93.5 % )。EPAS1/HIF 2α与肿瘤的病理分级 (r =0 .86 2 ,P <0 .0 0 1)和临床分期 (r=0 .80 5 ,P <0 .0 0 1)密切相关。 6 0例膀胱癌标本中VEGF阳性表达 4 4例。病理分级Ⅰ级标本阳性表达 12例 (42 .8% ) ,Ⅱ级 12例、Ⅲ级 19例均阳性表达。浅表性膀胱癌中阳性表达 14例 (48.3% ) ,浸润性癌中阳性表达 30例 (96 .8% ) ,VEGF表达与肿瘤病理分级 (r=0 .84 1,P <0 .0 0 1)和临床分期 (r =0 .819,P <0 .0 0 1)密切相关。EPAS1/HIF 2α表达与VEGF表达密切相关 (r=     

肾透明细胞癌组织中泛素连接酶Pirh2蛋白的表达及其临床意义

目的 探讨肾透明细胞癌组织中泛素连接酶Pirh2蛋白(p53-induced RING-H2 protein,Pirh2)的表达及与临床病理特征和预后的关系. 方法 肾透明细胞癌标本92例,G1 29例、G2 36例、G3 24例、G4 3例,T1 55例、T2 16例、T3 20例、T4 1例;正常肾组织标本20例作为对照组.采用免疫组织化学方法检测两组标本组织中Pirh2蛋白的表达,并结合临床资料进行分析. 结果 正常肾组织中Pirh2蛋白表达率为20.0％ (4/20),肿瘤组织为52.2％(48/92),且随组织病理分级和分期增加,Pirh2蛋白表达量逐渐增高.Pirh2蛋白在G1、G2、G3、G4组织中的高表达阳性率分别为24.1％、30.6％、75.0％和66.7％,T1、T2、T3、T4期肿瘤组织中高表达阳性率分别为25.5％、50.0％、75.0％和100.0％,分级间分期间差异有统计学意义(P=0.001).随访7～70个月,平均42个月,复发10例,复发组与未复发组中 Pirh2蛋白高表达阳性率分别为80.0％和36.6％,差异有统计学意义(P=0.022).Kaplan-Meier曲线显示,Pirh2蛋白高表达组与低表达组患者术后总生存率(71.1％与94.4％)和无复发生存率(78.9％与96.3％)比较,差异均有统计学意义(P＜0.01). 结论 Pirh2蛋白高表达与肾透明细胞癌的恶性程度及预后相关,Pirh2与肾透明细胞癌的发生和发展存在相关性.     

膀胱癌组织MMP-9和TIMP-1的表达及其意义

目的　研究金属蛋白酶 9(MMP 9)及其抑制因子 (TIMP 1)在膀胱癌中的表达及其临床意义。方法　应用免疫组化方法检测MMP 9及TIMP 1在 6 5例膀胱癌和 19例非肿瘤性膀胱组织中的表达。结果　MMP 9在膀胱癌细胞和间质组织中均有表达 ,而TIMP 1主要表达在膀胱癌细胞中 ,在间质组织中很少表达。TIMP 1在膀胱癌细胞中的表达低于非肿瘤性膀胱组织中移行上皮的表达 ,两者差别有统计学意义 (P <0 .0 5 ) ,但与膀胱癌的病理分级、分期无统计学相关性 (P >0 .0 5 )。MMP 9在膀胱癌细胞及间质中的表达均高于非肿瘤性膀胱组织 ,两者差别有统计学意义 (P <0 .0 5 ) ,而且与膀胱癌的病理分级、分期均呈正相关 (P <0 .0 5 )。膀胱癌细胞表达TIMP 1与间质组织表达MMP 9呈负相关 (P <0 .0 5 ) ,MMP 9及TIMP 1的表达与肿瘤的复发、多发均无相关性 (P >0 .0 5 )。结论　MMP 9和TIMP 1参与膀胱癌的浸润和转移 ,对预后判断、诊断及治疗具有一定的意义。     

Liver and serum expression of matrix metalloproteinases in asymptomatic pediatric liver transplant recipients

We related hepatic gene and serum expression of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) to liver histology in pediatric LT recipients. Liver biopsies and serum samples were obtained from 52 patients 10.6 years post‐LT and age‐matched controls for analyses of MMPs and TIMPs. Patients with fibrosis had significantly higher hepatic gene expression of MMP‐2, MMP‐9, MMP‐14, TIMP‐1, and TIMP‐2 than patients without. Expression of these genes correlated with graft Metavir fibrosis stage (r = 0.494–0.684, P ≤ 0.006 for all). Gene expression of MMP‐1, MMP‐3, MMP‐8, TIMP‐3, and TIMP‐4 was undetectable in both patients and controls. Portal inflammation and cytokeratin 7 correlated positively with gene expression of TIMP‐1. Gene expression of MMP‐2, MMP‐9, and TIMP‐2 correlated negatively with the time of low‐dose cortisone usage (r = ?0.448 to ?0.422, P < 0.05 for all). Serum concentrations of MMP‐8 and TIMP‐1 were significantly increased and MMP‐9 decreased among patients compared with controls, but no correlations to graft histology or gene expression were observed. Hepatic gene expression of certain MMPs and TIMPs is increased in stable pediatric LT recipients displaying graft fibrosis, but this did not reflect to their serum concentrations. Increased hepatic gene expression of TIMP‐1 correlated with graft fibrosis stage, inflammation, and chronic cholestasis.     

肾嫌色细胞癌(附15例报告)

目的　提高肾嫌色细胞癌的诊治水平和对此类型肾癌的认识。　方法　回顾性分析15例肾嫌色细胞癌的临床资料。男 10例 ,女 5例。年龄 4 7～ 74岁 ,平均 5 7岁。均行根治性肾切除术。　结果　术后病理证实为肾嫌色细胞癌。病理分期 :pT1N0 M0 6例 ,pT2 N0 M0 5例 ,pT3bN0 M0 2例 ,pT1N2 M0 1例 ,pT2 N2 M0 1例。病理分级 :G2 10例 ,G3 5例。 11例获随访 ,随访 2～ 31个月 ,平均19个月 ,1例死于心脏病 ,1例局部复发 ,9例无瘤生存。　结论　肾嫌色细胞癌是一种具有特殊形态的少见肾癌类型。肾根治性切除术是治疗肾嫌色细胞癌的首选方法。与同期、同级的其他类型肾癌相比 ,肾嫌色细胞癌预后较好。     

肾嫌色细胞癌21例临床分析及文献复习

目的 提高肾嫌色细胞癌的诊治水平和对此类型肾癌的认识.方法 回顾性分析21例肾嫌色细胞癌的临床资料.男11例,女10例.年龄27 ～ 85岁,平均52岁.11例行腹腔镜下肾癌根治术,8例行腹腔镜下肾部分切除术,2例行开放肾癌根治术.结果 术后病理证实为肾嫌色细胞癌.病理分期:pT1N0M0 13例,pT2N0M0 5例,pT3aN1 M0 2例,pT4N0M0 1例.Fuhrman病理分级:G1 6例,G2 14例,G31例.术后随访19例,时间3～36个月,平均17个月,1例死于心脏病,1例术后6个月局部复发,给予索拉非尼治疗2个月后肺部感染死亡,1例术后12个月后出现肺转移,给予索拉非尼治疗1个月后死亡,16例无瘤生存.结论 肾嫌色细胞癌是一种具有特殊形态的少见肾癌类型.肾根治性切除术是治疗肾嫌色细胞癌的首选方法.与同期、同级的其他类型肾癌相比,肾嫌色细胞癌预后较好.     

Plasma concentrations of metalloproteinases (MMP-1, MMP-3) and their inhibitors in patients with prostate cancer

Summary Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in important processes of tumor invasion and metastasis. In the study presented, matrix metalloproteinase 1 (MMP1) and 3 (MMP3), the tissue inhibitor of metalloproteinase 1 (TIMP1) and the complex MMP1/TIMP1 were measured by ELISA tests specific for these proteins in blood plasma. These components have been investigated in prostate cancer patients (PCa) with metastases (n = 18; T2, 3, 4 pN1, 2M1), prostate cancer patients without metastases (n = 29; T2, 3 pN0M0), patients with benign prostate hyperplasia (BPH; n = 29) and in healthy men (n = 35). Mean values of MMP1 and of the complex MMP1/TIMP1 were not different among the four groups. The mean values of MMP3 and especially TIMP1 were significantly higher in prostate cancer patients with metastases compared with controls, BPH patients and prostate cancer patients without metastases. Ten of these 18 patients had TIMP1 levels higher than the upper reference limit. TIMP1 concentrations correlate to the tumor stage but not to the tumor grade. These results indicate, that TIMP1 could be an potential marker for metastases in prostate cancer patients.      

Circulating levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with incisional hernia

Incisional hernia formation is a common complication to laparotomy and possibly associated with alterations in connective tissue metabolism. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are closely involved in the metabolism of the extracellular matrix. Our aim was to study serum levels of multiple MMPs and TIMPs in patients with and without incisional hernia. Out of 305 patients who underwent laparotomy, 79 (25.9%) developed incisional hernia over a median follow‐up period of 3.7 years. Pooled sera from a subset (n = 72) of these patients were screened for MMP‐1, MMP‐2, MMP‐3, MMP‐7, MMP‐8, MMP‐9, MMP‐10, MMP‐12, MMP‐13, TIMP‐1, TIMP‐2, and TIMP‐4 using a multiplex sandwich fluorescent immunoassay supplemented with gelatin zymography. The screening indicated differences in serum MMP‐9 and TIMP‐1 levels. Consequently, MMP‐9 and TIMP‐1 levels were measured in serum in the whole patient cohort with enzyme‐linked immunosorbent assay. There were no significant differences in either MMP‐9 (p = 0.411) or TIMP‐1 (p = 0.679) levels between hernia and hernia‐free patients. MMP‐9 was significantly increased in smokers compared with nonsmokers (p = 0.016). In conclusion, a possible involvement of MMPs and TIMPs in the pathogenesis of incisional hernia formation was not reflected systemically.     

Role of gelatinases (matrix metalloproteinases 2 and 9), vascular endothelial growth factor and endostatin on clinicopathological behaviour of rectal cancer

Aim The aim of this study was to evaluate the role of matrix metalloproteinases (MMPs), their tissue inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] and activators [membrane‐type MMPs (MT1‐MMPs)], vascular endothelial growth factor (VEGF) and endostatin on clinicopathological variables and prognosis in patients with rectal cancer. Method Paired samples of tumour tissue and normal tissue were obtained from patients with rectal cancer who underwent curative surgery (n = 34). Gelatin zymography for MMP‐2 and MMP‐9, an activity assay for MT1‐MMP and enzyme‐linked immunoassays for TIMP‐2, VEGF and endostatin were performed using extracts from the paired tissue samples. Results Active MMP‐9 showed statistically significant relationships with metastatic disease and perineural invasion (P = 0.002 and P = 0.042). A significant relationship was observed between the levels of tumoral pro‐MMP‐2 and pro‐MMP‐9 and the presence of lymph node metastasis (P = 0.012 and P = 0.021, respectively). Tumoral TIMP‐2 levels showed a significant relationship with tumour recurrence (P = 0.011). A significant relationship was also observed between tumour VEGF levels and the presence of perineural invasion (P = 0.044), and VEGF levels were correlated with the size of the tumour (P = 0.009, r = 0.454). Conclusion These results might contribute to further investigation of a possible prognostic significance in rectal cancer.