P-gp、GST-π和TOPO-II在乳腺癌原发灶和复发灶中的表达

目的分析乳腺癌复发患者原发灶和复发灶中P-gp、GST-π、TOPO-Ⅱ的表达及其临床意义。方法收集2008年1月至2010年12月江苏省肿瘤医院收治的55例局部复发的乳腺患者,用免疫组化方法检测55例乳腺癌原发灶和复发灶中P-gp、GST-π、TOPO-Ⅱ的表达。结果原发灶和复发灶中P-gp、GST-π、TOPO-Ⅱ的阳性表达率分别为63.6%、34.5%、45.5%和90.9%、41.8%、40.0%,仅P-gp表达在原发灶和复发灶之间差异有统计学意义(P<0.05)。3种蛋白中有至少2种共同表达的病例数在原发灶中为13例,在复发灶中有19例。结论乳腺癌原发灶与复发灶中多种耐药基因蛋白表达存在明显差异,复发灶中耐药基因蛋白表达更高,应引起临床重视。     

MDR相关蛋白在口腔鳞癌的表达及其临床意义

目的 检测口腔鳞癌患者化疗前后P-糖蛋白(P-gp)、肺耐药相关蛋白(LRP)、多药耐药相关蛋白(MRP)、拓朴异构酶Ⅱα(TopoⅡα)的蛋白质表达,分析其与临床病理参数及化疗敏感性的关系。方法 采用流式细胞术的方法,对34例口腔鳞癌患者术前诱导化疗前后P-gp,LRP,MRP,TopoⅡα的蛋白质表达进行测定。化疗方案为平阳霉素16mg/m2,第1-10天。结果 ①口腔鳞癌临床化疗有效率为20.6％,其中CR 1例、PR 6例、NC 26例、PD 1例。多因素分析结果表明P-gp的表达水平与口腔鳞癌对平阳霉素化疗的敏感性呈负相关(P=0.041),而LRP,MRP,TopoⅡα的蛋白质表达均与化疗反应无明显的相关性;同时单因素分析发现化疗有效者的P-gp表达水平明显低于无效者(P<0.05),而LRP、MRP及TopoⅡα蛋白质表达在二者并无显著差异;②在口腔鳞癌组织中,同时存在多种MDR相关蛋白超表达的现象,其中P-gp平均表达率为27.7％±30.2％,LRP为41.1％±17.9％,MRF为43.9％±16.1％;癌组织的MDR相关蛋白表达水平明显高于癌旁组织(P<0.05),同时,它们在化疗前后的表达水平并无显著差异,表明口腔鳞癌的多药耐药性与内在性耐药有关;③P-gp的表达水平与肿瘤细胞的分化程度呈正相关(P<0.05),分化越好,表达水平也越高(P<0.05),但与临床分期、淋巴结转移无关;而LRP、MRP     

胃癌转移淋巴结奥沙利铂体外化疗药敏性与多种耐药相关因子表达的关系

目的:探讨胃癌淋巴结转移灶肿瘤细胞对奥沙利铂的体外化疗药敏性与多种多药耐药相关因子表达的关系.方法:分离提取54例胃癌新鲜肿瘤组织及转移淋巴结中的肿瘤细胞,进行肿瘤细胞培养化疗药敏性实验,同时用免疫组织化学法检测原发灶、淋巴结转移灶多药耐药相关因子P-gp、GST-π、p53、Survivin和Bcl-2的表达.结果:奥沙利铂对胃癌淋巴结转移灶肿瘤细胞的抑制率低于原发灶(P<0.05).P-gp、GST-π和Bcl-2在淋巴结转移灶中表达程度均高于原发灶(P均<0.05),而p53和Survivin在肿瘤原发灶、转移灶中的表达强度无显著性差异(P均>0.05);P-gp、p53、Bcl-2表达在胃癌原发灶、淋巴结转移灶中均呈正相关(γ分别为0.3424、0.7123、0.4548,P均<0.05),而GST-π、Survivin在两种组织间表达强度无明显相关性(P均>0.05).胃癌原发灶奥沙利铂对肿瘤细胞的药物抑制率与P-gp、GST-π和Survivin表达强度呈负相关(P均<0.05),三者对药物抑制率影响作用依次为GST-π>P-gp>Survivin;转移淋巴结中仅发现Survivin表达强度对药物抑制率有影响,与药物抑制率呈负相关(P<0.05).结论:胃癌淋巴结转移灶中,奥沙利铂对肿瘤细胞抑制率和多药耐药相关因子的表达均显示出与原发灶不同的异质性变化,肿瘤原发灶与转移灶中影响奥沙利铂药敏性的主要因子也不相同,术后辅助化疗及实现多药耐药逆转应针对淋巴结转移灶进行.     

食管癌组织中P53、P-gp等蛋白的表达

目的检测食管癌组织中P53、多药耐药基因(mu ltidrug resistance gene1,MDR1)及其编码产物P-糖蛋白(p-glycoprote in,P-gp)、肺耐药蛋白(lung resistance prote in,LRP)、谷胱甘肽S-转移酶(glutath ione S-transferase,GST-π)、拓扑异构酶(topoisom eraseⅡ,TopoⅡ)的表达水平,探讨其与临床分期、分化程度、淋巴结转移、肿瘤浸润深度及病理分型的关系。方法采用免疫组织化学技术检测P53、MDR1、LRP、GST-π、TopoⅡ基因的表达水平。结果66例标本中,P53、MDR1、LRP、GST-π、TopoⅡ基因阳性表达率分别为65.2%(43/66)、97.0%(64/66)、84.8%(56/66)、60.6%(40/66)、37.9%(25/66)。食管癌不同组织学分级的TOPOⅡ表达率不同,高分化的表达率高于中低分化者,但不具显著性差异(P=0.05)。LRP的阳性表达率在不同浸润深度之间有显著性差异。P-gp的阳性表达率在溃疡型食管鳞状细胞癌中明显高于其他两种类型,有显著性差异,P=0.003。结论食管癌组织中P53、MDR1、LRP、GST-π、TopoⅡ基因存在高表达;肿瘤组织分化越高,TopoⅡ表达率越高;肿瘤浸润越深,LRP阳性表达率越高。这些检测对临床化疗药物选择可起一定指导作用。     

食管鳞癌组织GST-π和TOPO-Ⅱ表达及其相关性研究

目的:研究食管鳞癌组织谷胱甘肽S-转移酶-π(GST-π)和DNA拓扑异构酶Ⅱ(TOPO-Ⅱ)表达及其相关性研究.方法:应用免疫组化SP法检测GST-π和TOPO-Ⅱ48例食管鳞癌组织和30例正常黏膜组织中的表达.结果:在正常食管黏膜和食管鳞癌组织中GST-π和TOPO-Ⅱ的阳性表达率分别为30.00%(9/30)、20.00%(6/30)和64.58%(31/48)、41.67%(20/48);食管鳞癌组织和正常食管黏膜比较差异均有统计学意义,P＜0.05.GST-π和TOPO-Ⅱ的表达与淋巴结转移无关;与分化程度有关;GST-丌与TOPO-Ⅱ的表达呈负相关(r=-0.787,P＜0.05).结论:联合检测GST-π和TOPO-Ⅱ可以作为判断食管癌浸润、转移能力的有效指标.同时可应用于预测患者临床化疗的敏感性,筛选出不具有耐药的联合方案,提高疗效.     

胃癌组织中多药耐药相关蛋白mRNA的表达及MDR基因产物的检测与其临床病理关系的研究

目的通过对胃癌组织中MRP1mRNA,MRP2mRNA的表达水平及MDR基因产物的检测,进一步了解肿瘤多药耐药机制与胃癌发生发展、生物学行为和预后的关系。方法胃癌组织中MRP1mRNA,MRP2mRNA的表达采用原位杂交染色法。MDR基因产物的检测应用SP免疫组织化学法。结果67例胃癌组织中MRP1mRNA和MRP2mRNA表达阳性率分别为68.7%和71.6%,高分化腺癌和区域淋巴结未转移癌中MRP1mRNA和MRP2mRNA表达阳性率明显高于未分化腺癌和伴淋巴结转移癌(P<0.05,P<0.01),而且不同组织类型中MDR基因产物P170(P-gp),GS T-π及TOPO-Ⅱ的表达不同,有淋巴结转移的胃癌患者P-gp的表达较高,而GS T-π及TOPO-Ⅱ的表达与有无淋巴结转移无关。结论MRP1mRNA和MRP2mR-NA的表达水平与MDR基因产物的分配有密切关系,检测胃癌组织中多药耐药相关蛋白mRNA表达的同时检测MDR基因产物对了解胃癌的发生发展、生物学行为和预后,以及指导化疗均具有重要的临床意义。     

耐药相关基因在非小细胞肺癌组织中的表达及其意义

目的:探讨耐药相关基因在非小细胞肺癌(NSCLC)组织中的表达及其临床意义.方法:应用免疫组化技术检测治疗前肺癌组织标本中P-gp、MRP、LRP、GST-π和TopoⅡ表达.结果:58例治疗前NSCLC中P-gp、MRP、LRP、GST-π和TopoⅡ阳性率分别为96.55%,67.24%,75.86%,65.52%,98.28%,并有部分共表达.癌旁正常肺组织呈阴性或弱阳性表达.性别、有无吸烟史、有无淋巴结转移及在TNM各分期中P-gp、MRP、LRP、GST-π和TopoⅡ阳性表达无明显差异(P＞0.05).比较腺癌组与鳞癌组,MRP、LRP、GST-π阳性表达有显著性差异(P＜0.05),而P-gp、TopoⅡ阳性表达无明显差异(P＞0.05);MRP、LRP、P-gp、GST-π共表达有显著性差异(χ2=21.662,P＜0.001);低分化腺癌、鳞癌与中、高分化腺癌、鳞癌P-gp、MRP、LRP、GST-π和TopoⅡ阳性表达无明显差异(P＞0.05).结论:肺癌耐药为一多途径多基因参与的过程,肺腺癌原发的多药耐药机率较肺鳞癌高,联合检测肺癌组织中耐药相关基因的表达有助于判断化疗疗效及预后.     

结肠癌转移性淋巴结COX-2和P-gp及Survivin表达意义的探讨

目的:探讨COX-2、P-gp及Survivin在结肠癌淋巴结转移灶中的表达情况及其意义。方法:对45例伴淋巴结转移的结肠癌手术标本的原发灶及转移淋巴结进行COX-2、P-gp、Survivin免疫组化染色,比较其在淋巴结转移灶与原发灶的表达差异,并进行相关分析。结果:COX-2、P-gp及Survivin在原发灶中强表达率分别为48.9%、64.4%和62.2%;3种蛋白在转移灶中强表达率分别为71.1%、80.0%和66.7%。COX-2、P-gp在转移灶中的表达高于原发灶(χ2分别为5.556和4.455,P分别为0.018和0.035);COX-2、P-gp在转移灶与原发灶中的表达具有正相关性(rs分别为0.392 8和0.652 4,P分别为0.008和<0.000 1)。在原发灶中,COX-2与Survivin间表达强度具有明显正相关性(rs=0.688 6,P<0.000 1);在转移灶中,COX-2与P-gp之间表达强度具有正相关性(rs=0.319 9,P=0.032)。结论:对结肠癌淋巴结转移灶中COX-2、P-gp及Survivin的检测反映出肿瘤在转移过程中的异质性,对肿瘤多药耐药性的...     

鼻咽癌组织中P-gp、MRP和LRP的表达及其临床意义

目的探讨多药耐药基因蛋白(P-gp)、多药耐药相关蛋白(MRP)和肺耐药相关蛋白(LRP)在鼻咽癌组织中的表达情况及其临床意义。方法应用单克隆抗体多药耐药相关蛋白(P-gp),多药耐药基因蛋白(MRP),肺耐药相关蛋白(LRP),对54例鼻咽癌初诊患者的肿瘤组织进行免疫组化检测。结果3项多药耐药指标在54例患者中有不同程度表达。P-gp、MRP、LRP的表达与鼻咽癌病理类型、临床分期及有无淋巴结转移不相关;P-gp表达与MRP、LRP表达不相关,MRP与LRP表达间呈正相关。结论联合检测LP-gp、MRP、LRP在鼻咽癌组织中的表达,对鼻咽癌化疗药物的选择及预后的判断都有重要的参考价值。     

P-糖蛋白和肺耐药蛋白在浸润性乳腺癌中的表达及其临床意义

目的探讨P-糖蛋白(P-gp)和肺耐药蛋白(LRP)在浸润性乳腺癌中的表达情况及其临床意义。方法采用搓网法获取乳腺癌手术切除标本制成的完整单细胞悬液,再用流式细胞技术对40例乳腺癌组织及相应癌旁组织中P-gp、LRP的表达情况进行定量分析。结果乳腺癌组织P-gp、LRP表达与相应癌旁组织比较,差异均有统计学意义(P-gp:t=-7.777,LRP:t=-9.861,P均0.050)。在不同年龄、肿瘤大小、病理类型、临床分期、分化程度和雌、孕激素受体状态的患者间,两种耐药相关蛋白的表达差异均无统计学意义(P0.050)。有淋巴结转移组P-gp表达与无淋巴结转移组比较,差异无统计学意义(t=0.102,P=0.919)。有淋巴结转移组LRP的表达为(41.2±18.5)%,无淋巴结转移组为(30.1±15.4)%,有淋巴结转移组LRP表达显著高于无淋巴结转移组(t=2.074,P=0.045)。乳腺癌组织P-gp与LRP的表达间存在正相关性(r=0.698,P0.001)。结论本研究结果可为寻找浸润性乳腺癌的有效辅助化疗药物提供参考。     

Multidrug Resistance in Primary Tumors and Metastases in Patients with Esophageal Squamous Cell Carcinoma

Studies have demonstrated that radical esophagectomy can significantly prolong disease-free survival and improve the survival rate of patients with T3 or T4 esophageal cancer and lymph node metastasis. Multidrug resistant cancer cells have active efflux mechanisms that prevent the accumulation of chemotherapeutic drugs in the cells. The purpose of this study was to compare the expression of five MDR related proteins between primary tumors in patients with thoracic esophageal squamous cell carcinoma (ESCC) and metastatic cancer in lymph nodes to explore the clinical significance of heterogeneity in MDR metastatic cancer cells. Fifty-four patients with ESCC and lymph node metastasis were included. All patients underwent subtotal esophagectomy and D2/D3 lymph node resection. The expression of lung resistance-related protein (LRP), P-glycoprotein, topoisomerase-II, thymidylate synthase, and glutathione S-transferase P1–1 (GST-π) were determined in the primary tumors and lymph nodes via immunohistochemistry. The expression of LRP was significantly different between the primary tumors and lymph nodes (P?=?0.026). No significant differences were found for the other four proteins, and protein expression was not associated with either degree of differentiation or disease stage. It was also found that GST-π was expressed in all patients in both the primary tumors and lymph nodes, suggesting that the design and application of chemotherapeutic protocols capable of reducing GST-π expression may be beneficial for patients with ESCC. Additional research regarding the clinical utility of MDR protein expression in ESCC is warranted to design effective chemotherapeutic protocols.     

非霍奇金淋巴瘤多药耐药蛋白在淋巴结与骨髓液中表达的实验研究

 目的　探讨初发非霍奇金淋巴瘤（NHL）骨髓液和淋巴结活组织两种标本中多药耐药蛋白的表达及临床价值评估。方法　采用流式细胞术（FCM）活细胞免疫荧光法检测41例初治NHL淋巴结活组织中和37例骨髓液中瘤细胞多药耐药蛋白及反转录-聚合酶链反应（RT-PCR）半定量检测mdr1mRNA的表达,分析其与临床分期、恶性分级、乳酸脱氢酶（LDH）异常增高等的相关性。结果　两种标本中三种耐药基因单独及联合过度表达率无明显差异;淋巴结组织中,P-gp阳性表达在Ⅰ／Ⅱ期和Ⅲ／Ⅳ期之间有差别（P＝0.046）,与LDH异常增高相关（P＜0.05）,与恶性度分级无关（P＞0.1）;肺耐药蛋白（LRP）与三者都存在明显相关（P＜0.05）。而骨髓液中仅LRP与恶性分级和LDH异常增高明显相关（P＝0.01）,并未显示P-gp表达在不同分期的差异性;淋巴结中P-gp+的CR低于P-gp-（37.5 %,84.8 %;P＜0.01）;LRP+与LRP-的CR之间亦存在差别（53.3 %,88.5 %;P＜0.01）。结论　用淋巴结活组织进行耐药蛋白检测比骨髓能提供更准确的临床信息,且在肿瘤尚未发生骨髓转移时,取淋巴组织亦能进行耐药蛋白检测,及早指导临床治疗及预后。     

Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins.

PURPOSE: Several studies have reported clinical behavior and chemotherapy resistance in leiomyosarcomas, but these studies did not differentiate between soft tissue leiomyosarcomas (LMS) and malignant gastrointestinal stromal tumors (GIST). Multidrug resistance (MDR) has been associated with the expression of P-glycoprotein (P-gp), multidrug resistance protein (MRP(1)), and lung resistance protein (LRP). The aim of the present study was to compare LMS and GIST with respect to clinical outcome and MDR parameters. PATIENTS AND METHODS: Clinical outcome was evaluated in 29 patients with a primary deep-seated LMS and 26 patients with a primary malignant GIST. Paraffin-embedded material, available for 26 patients with LMS and 25 with GIST, was used for immunohistochemical detection of P-gp, MRP(1), LRP, and c-kit. RESULTS: Mean overall survival (OS) was 72 months for LMS patients and 31 months for GIST patients (P: <.05). Metastases occurred in 16 (59%) of 27 assessable LMS patients and in 10 (56%) of 18 assessable GIST patients. LMS predominantly metastasized to the lungs (14 of 16 patients), whereas GIST tended to spread to the liver (five of 10 patients) and the abdominal cavity (three of 10 patients; P: <.001). P-gp and MRP(1) expression was more pronounced in GIST than in LMS (P: <.05): the mean percentage of P-gp expressing cells was 13.4% in patients with LMS and 38.4% in patients with GIST, and the mean percentage MRP(1) expressing cells was 13.3% in patients with LMS and 35.4% in patients with GIST. LRP expression did not differ between LMS and GIST. c-kit was expressed in 5% of the LMS patients and in 68% of the GIST patients. CONCLUSION: LMS patients have a better survival than GIST patients, and the metastatic pattern is different. Expression of MDR proteins in LMS is less pronounced than in GIST.     

Further evidence that altered p16/CDKN2 gene expression is associated with lymph node metastasis in squamous cell carcinoma of the esophagus

Esophageal squamous cell carcinoma (ESCC) has high malignant potential with a poor outcome. Lymph node metastasis is the most useful indicator for predicting the outcome of ESCC. The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively regulate CDK4-mediated phosphorylation of RB protein in the cell cycle. We immunohistochemically detected p16, cyclin D1, and RB expressions in both primary lesions and metastatic lymph nodes in ESCC. Among the 50 ESCC primary lesions, 24 (48%) were positive for p16, while 26 (52%) were negative for p16. Sixteen (32%) were p16-positive, 34 (68%) were p16-negative among the 50 ESCC metastatic lymph nodes. Eight cases (16%) were p16-positive in primary lesion and p16-negative in lymph node, however, no cases that was p16-negative in the primary tumor exhibited p16-positivity in metastatic lymph nodes (p < 0.0001). Seventeen (34%) of the 50 ESCC primary lesions were cyclin D1-positive, while 33 (66%) were cyclin D1-negative. Twenty-four (48%) were cyclin D1-positive, 26 (52%) were cyclin D1-negative among the 50 metastatic lymph nodes. Five cases (10%) were cyclin D1-positive in primary lesion and cyclin D1-negative in lymph node, and 12 cases (24%) were cyclin D1-negative in primary lesion and cyclin D1-positive in lymph nodes. Nine cases (18%) were RB-negative in 50 primary lesions, and the rate of loss of RB expression in metastatic lymph nodes was not markedly higher than in primary lesions. Thirty-nine (78%) of 50 primary lesions and 46 (92%) of 50 metastatic lymph nodes had altered expression of at least one of the three G1 control genes. Tumor cell with disruption of these cell cycle regulators can get a growth advantage and metastatic potential during tumor progression, especially p16/CDKN2 alterations may be associated with lymph node metastasis in ESCC. These results also suggest that tumor cells in metastatic lymph nodes may have more aggressive proliferation and higher malignant potential than tumor cells in primary lesions.     

P-糖蛋白与肺耐药蛋白在乳腺癌组织中的表达及其与预后的关系

背景与目的:肿瘤细胞的多药耐药(multidrugresistance,MDR)现象是化疗失败的常见原因。P-糖蛋白(P-glycoprotein,P-gp)和肺耐药蛋白(lungresistanceprotein,LRP)的过度表达在乳腺癌的MDR中起着重要作用。本研究探讨P-gp与LRP在乳腺癌组织中的表达及其与预后的关系。方法:采用免疫组织化学LSAB法检测151例乳腺癌石蜡包埋组织和40例乳腺正常组织的P-gp和LRP表达水平,并将结果与临床病理资料和预后结合起来进行分析。结果:在151例乳腺癌组织中P-gp阳性62例(40.8%),40例正常乳腺组织中P-gp阳性1例(2.5%),两组间差异有显著性(χ2=21.27,P<0.01);151例乳腺癌组织中LRP阳性121例(80.1%),40例正常乳腺组织中LRP阳性22例(55.0%),两组间差异有显著性(χ2=10.62,P<0.01)。P-gp表达与患者年龄、肿块大小、组织学类型、淋巴结转移、组织学分级、临床分期、ER状态和预后等因素无关。在有淋巴结转移的70例乳腺癌组织中LRP阳性62例(88.6%),无转移的81例中LRP阳性59例(72.8%),两组间差异有显著性(χ2=4.891,P<0.05)。在LRP阳性的121例乳腺癌组织中中P-gp阳性55例(45.5%),LRP阴性的30例中P-gp阳性7例(23.3%),两组间差异有显著性(χ2=3.990,P<0.05)。LRP的表达与淋巴结转移(r=0.197,P<0.05)和P-gp表达(r=0.179,P<0.05)呈正     

Immunohistochemical expression of multidrug resistance proteins as a predictor of poor response to chemotherapy and prognosis in patients with nodal diffuse large B-cell lymphoma

BACKGROUND/AIMS: The aim of this study was to determine whether expression of P-glycoprotein (P-gp), multidrug-resistance-related protein 1 (MRP1), and lung resistance protein (LRP) was related to the response to induction chemotherapy and prognosis in untreated diffuse large B-cell lymphoma (DLBCL). METHODS: We assessed immunohistochemical expression of P-gp, MRP1 and LRP, using formalin-fixed and paraffin-embedded specimens of lymph node in 41 patients with DLBCL. Association between expression of these three proteins and their impact on clinical outcome and prognosis was statistically evaluated. RESULTS: P-gp was positive in 37% of subjects, MRP1 in 63%, and LRP in 68%. The complete remission rates achieved in the group expressing these multidrug resistance (MDR) proteins was significantly lower than in the group not expressing them (20 versus 58%; p = 0.025 in P-gp, 23 versus 80%; p < 0.001 in MRP1 and 32 versus 69%, p = 0.043 in LRP, respectively). Furthermore, the patients expressing LRP had a shorter overall survival rate than those that did not (median of 26 months versus median not reached; p = 0.013). CONCLUSIONS: These findings suggest that the three MDR proteins are important predictive factors for the clinical outcome and prognosis in patients with DLBCL.     

Multidrug resistance proteins in primary and metastatic soft-tissue sarcomas: down-regulation of P-glycoprotein during metastatic progression

BACKGROUND: Chemotherapy sensitivity of soft-tissue sarcomas (STS) is limited, which may be due to multidrug resistance (MDR). MDR is associated with expression of P-glycoprotein (P-gp), Multidrug Resistance-associated Protein 1 (MRP1) and Lung Resistance-related Protein (LRP). It is unknown whether in STS metastasis is more resistant than the primary counterpart. MATERIALS AND METHODS: In 35 chemonaive STS and their metastases (86% chemonaive), MDR proteins were immunohistochemically assessed. Eleven metastases presented synchronously, 24 metachronously. Expression was scored positive (>5% positive tumour cells) or negative. RESULTS: P-gp was positive in 31/34 primaries (91%), versus 22/32 metastases (69%) (p=0.005). This difference was significant for metachronous metastases (p=0.008). MRP1 was positive in 18/32 primaries (56%) and 22/33 metastases (67%). MRP1 was more expressed in synchronous metastases than primaries (p=0.047), but for the overall group this significance disappeared. LRP expression did not differ: 27/34 primaries (80%), versus 28/34 metastases (82%). CONCLUSION: P-gp, MRP1, LRP expression in the primary tumours was high. Metastatic progression did not coincide with MDR-protein up-regulation.     

食管癌原发灶与淋巴结转移灶细胞染色体变化特征的比较

背景与目的:食管癌早期可发生局部淋巴或血行转移,这是导致复发和预后差的主要原因。但是,食管癌转移发生的分子机制尚不清楚。本研究旨在分析食管癌原发灶和淋巴结转移灶肿瘤细胞染色体变化的特征,寻找或定位与食管癌转移相关基因,加深对其转移机制的了解。方法:应用比较基因组杂交技术(comparativegenomichybridization,CGH)分析15例食管癌患者原发灶和其对应的淋巴结转移灶的染色体基因组改变。结果:最常见染色体DNA拷贝数增加的部位是3q,8q,6p,20p,5p,18p,2p,2q,1q;常见的染色体DNA拷贝数丢失的部位是10p,10q,17p,18q,4p,13q。其中,最有意义的发现是6p增加(原发灶:2/15,13%,转移灶:7/15,47%),20p增加(原发灶:5/15,33.3%,转移灶:11/15,73.3%)。第二个发现是10p丢失(原发灶:2/15,13.3%,转移灶:8/15,53%),10q丢失(原发灶:2/15,13.3%,转移灶:7/15,46.6%)。结论:食管癌原发灶和淋巴结转移灶细胞染色体基因组改变最显著的部位是6p,20p的增加和10p,10q的丢失;这些部位可能存在与食管癌细胞淋巴结转移相关的基因。     

多药耐药基因在原发性卵巢癌中的表达及意义

目的研究多个耐药基因P-糖蛋白（P-gp）、谷胱甘肽S转移酶（GST-π）、DNA拓扑异构酶-Ⅱ（Topo-Ⅱ）和肺耐药相关蛋白（LRP）在原发性卵巢癌中的表达,探讨其与卵巢癌患者耐药的关系。方法应用免疫组化SP法对80例卵巢癌、16例良性卵巢肿瘤及12例正常卵巢组织中P-gp、GST-π、Topo-Ⅱ和LRP表达情况进行测定。结果在卵巢癌中,P-gp、GST-π、Topo-Ⅱ、LRP阳性表达率分别为57.5%、58.8%、76.3%和73.8%,与正常卵巢组织和良性卵巢肿瘤组织中各自相应的基因蛋白阳性率比较差异均具有统计学意义（P〈0.05）。在良性卵巢肿瘤与正常卵巢组织中P-gp、GST-π、Topo-Ⅱ、LRP阳性表达率比较,差异也具有统计学意义（P〈0.05）。4种耐药相关蛋白存在共同表达现象,且具有不同的化疗反应性。P-gp、GST-π、LRP在卵巢癌中的表达与临床分期有关（P〈0.05）,Topo-Ⅱ则无关（P〉0.05）;P-gp、LRP与组织学分级无关（P〉0.05）,GST-π、Topo-Ⅱ则有关（P〈0.05）;P-gp、GST-π、Topo-Ⅱ、LRP与患者年龄、组织学类型、肿瘤大小、术后残余病灶大小均无关（P〉0.05）。结论卵巢癌存在原发性耐药并涉及多个耐药基因的共同表达。联合检测对预测化疗药物敏感性和判断化疗疗效具有指导意义。