胃腺癌患者癌组织中细胞周期素D1、p16及p27蛋白的表达及临床意义

目的探讨细胞周期相关调控因子细胞周期素(Cyclin)D1、p16及p27蛋白在胃腺癌组织中的表达及其患者癌与胃腺癌患者的临床病理学特征之间的关系。方法采用组织芯片技术制作经确诊的122例胃腺癌患者癌组织的组织芯片,通过免疫组化方法检测胃腺癌组织中CyclinD1、p16及p27蛋白的表达并分析三者与患者临床病理学特征之间的关系。结果 CyclinD1、p16及p27蛋白在胃腺癌组织中的阳性表达率分别为52.5%、27.9%和52.5%,与其在癌旁组织中的阳性表达率(分别为5.7%、78.7%和75.4%)有显著差异(均为P<0.01)。CyclinD1、p16及p27蛋白均与淋巴结转移有关(P值分别为0.001,0.011和0.046);CyclinD1和p16还与分化程度有关(P=0.015和P=0.028),但p27蛋白表达与分化程度无关;另外,p16蛋白表达还与肿瘤浸润深度有关(P=0.037)。CyclinD1阳性表达与p16和p27蛋白表达呈负相关关系,但p16和p27蛋白之间关系并不明显。结论 CyclinD1和p16、p27对胃腺癌患者预后评估均具有重要的意义,尤其是p16蛋白。     

Cyclin D1在乳腺肿瘤组织中的表达及其与基因扩增的相关性

目的研究细胞周期蛋白（Cyclin D1）表达在乳腺肿瘤发生中的作用及影响因素。方法采用免疫组化染色法检测122例乳腺恶性肿瘤和良性乳腺增生标本Cyclin D1表达；Southern杂交方法检测Cyclin D1基因变异。结果40例良性乳腺增生组织均未观察到Cyclin D1表达，40例浸润性导管癌组织、早期乳腺癌和淋巴结转移病变组织阳性率分别为55．0％（22／40）、52．0％（22／42）和53．3％（8／15）；25例浸润性导管癌组织Cyclin D1基因扩增率为16．0％，明显低于其蛋白表达率。结论Cyclin D1表达在乳腺癌发病早期即发挥作用，其在肿瘤发生、发展过程中的作用尚受基因扩增以外因素的影响。     

Cyclin D1在胃癌中的表达扩增及其生物学意义

目的：研究Cyclin D1蛋白的表达和基因的扩增及其与胃癌发生发展的关系。方法：采用免疫组化和差异聚合酶链反应（DPCR）技术对45例胃癌进行Cyclin D1检测。结果：Cyclin D1蛋白在胃癌中的表达率为57．8％（26／45），高于正常胃组织的20％（9／45），且与胃癌的分化和转移密切相关。胃癌组织Cyclin D1基因扩增的阳性率为48．9％（22／45）。DPCR和免疫组化结果基本一致。结论：Cyclin D1基因在胃癌的发生发展中起重要作用。Cyclin D1的表达和扩增与胃癌细胞的高增殖活性密切相关。     

口腔鳞癌组织中Cyclin D1、Ki-67基因的表达及意义

目的探讨口腔鳞癌组织中Cyclin D1、Ki-67基因蛋白表达与口腔鳞癌发生、发展的关系。方法取68份口腔鳞癌组织，用免疫组化法检测癌组织中Cyclin D1、Ki-67基因蛋白的表达，用积分PCR方法检测Cyclin D1的基因扩增。结果口腔鳞癌组织中Cyclin D1基因蛋白表达阳性36例(52．9％)，Ki-67基因蛋白表达阳性48例(70．5％)，Cyclin D1与Ki-67基因蛋白表达呈正相关(r=0．7861)，33份(48．5％)口腔鳞癌组织中Cyclin D1基因存在扩增，Cyclin D1基因扩增与Cyclin D1基因蛋白表达无相关性。Cyclin D1基因蛋白的表达与淋巴结转移有关，Ki-67基因蛋白的表达与肿瘤分化程度有关。结论Cyclin D1基因扩增及Ki-67基因蛋白表达水平可作为判断口腔鳞癌预后及其恶性程度的指标。     

胃癌组织中PTEN、Cyclin D1蛋白的表达变化及意义

目的观察胃癌组织中PTEN、Cyclin D1蛋白的表达变化,并探讨其临床意义。方法采用免疫组化SP法检测正常胃黏膜、慢性萎缩性胃炎、胃黏膜不典型增生及胃癌组织中的PTEN、Cyclin D1蛋白。结果癌旁正常胃黏膜组织中PTEN蛋白阳性率为95.24%、Cyclin D1蛋白阳性率为14.29%,慢性萎缩性胃炎组织中分别为81.48%、29.63%,胃黏膜不典型增生组织中分别为79.17%、37.50%,胃癌组织中分别为55.13%、62.82%,胃癌与其他各种胃黏膜组织比较,P均〈0.05。胃癌组织中PTEN和Cyclin D1蛋白的表达呈负相关（rs=-0.587,P〈0.01）。结论胃癌组织中PTEN蛋白低表达、Cyclin D1蛋白高表达,这可能是胃癌发生过程中的早期分子事件。     

非小细胞肺癌组织中Cyclin D1、p16蛋白的表达变化及意义

目的观察非小细胞肺癌(NSCLC)组织中Cyclin D1、p16蛋白的表达变化,并探讨其临床意义。方法采用免疫组化SP法检测96例NSCLC组织中的Cyclin D1蛋白和p16蛋白,以15例肺部正常组织作对照。结果在NSCLC组织、肺部正常组织中Cyclin D1蛋白呈阳性表达者分别为60、1例,p16蛋白呈阳性表达者分别为63、14例,两种组织相比,P均<0.05。Cyclin D1蛋白表达与NSCLC组织学分级及淋巴结转移有关(P均<0.05)。NSCLC组织中Cyclin D1蛋白与p16蛋白的表达呈负相关(rs=-0.298,P<0.01)。结论 NSCLC组织中Cyclin D1蛋白表达增强、p16蛋白表达减弱,Cyclin D1与p16存在互相抑制倾向,二者可能协同参与NSCLC的发生与发展过程。     

胃癌和癌旁组织中hMSH2和p27蛋白的表达及其意义

背景:错配修复(MMR)基因是保证DNA复制高保真度的重要基因,与消化道肿瘤的发生密切相关。抑癌基因p27可阻止细胞周期G1/S期转换,p27表达下调在肿瘤的进展、转移过程中起有一定作用。目的:探讨MMR基因hMSH2和p27在胃癌和癌旁组织中的表达及其意义。方法:以免疫组化方法检测93例胃癌患者癌组织和癌旁组织中hMSH2和p27蛋白的表达。结果:胃癌组织中hMSH2蛋白的阳性表达率为65.6%,显著高于癌旁组织的38.7%(P<0.01);p27蛋白的阳性表达率为46.2%,显著低于癌旁组织的80.6%(P<0.01)。胃癌组织中hMSH2蛋白的表达与肿瘤临床病理特征无相关性;p27蛋白的表达与肿瘤分化程度、浸润深度、淋巴结转移和TNM分期相关。hMSH2和p27蛋白在胃癌组织中的表达呈负相关。结论:MMR基因hMSH2表达异常和抑癌基因p27表达下调可能与胃癌的发生有关。     

胃癌组织中Cyclin E、p57与CDC25A的表达及意义

采用免疫组化SP法检测30例进展期胃癌组织、癌旁组织和10例正常胃组织中Cyclin E、p57与双重特异性磷酸酶A（CDC25A）的表达。结果在胃癌组织、癌旁组织和正常胃组织标本中p57的阳性表达率分别为40%（12/30）、73.3%（22/30）、90.0%（9/10）;Cyclin E的阳性表达率分别为70%（21/30）、36.7%（11/30）、10.0%（1/10）;CDC25A的阳性表达率分别为73.3%（22/30）、43.3%（13/30）、20.0%（2/10）。Cyclin E与CDC25A的表达呈正相关（r=0.371,P〈0.05）,p57与CDC25A的表达呈负相关（r=-0.412,P〈0.05）,p57与Cyclin E的表达呈负相关（r=-0.384,P〈0.05）。     

肺癌CDKN2基因产物表达的研究

目的观察ＣＤＫＮ２基因产物（Ｐ１６蛋白）在肺癌和癌旁正常组织的表达情况，了解该基因与肺癌的关系。方法采用ＳＰ免疫组织化学方法观察ＣＤＫＮ２基因产物在１３９例肺癌组织的表达情况，并与癌旁正常组织进行对比。结果Ｐ１６蛋白在良、恶性细胞的胞浆中均有表达，癌旁正常支气管粘膜上皮和浆液腺Ｐ１６蛋白的阳性率高于癌组织（Ｐ＜０．０１）。肺癌组织中Ｐ１６蛋白的总阳性率为６１．９％，腺癌的阳性率高于鳞癌和小细胞癌（Ｐ＜０．０１）。在鳞癌和腺癌Ｐ１６蛋白的阳性率随着分化程度的降低而下降，高分化和低分化腺癌之间Ｐ１６阳性率的差异有显著性（Ｐ＜０．０５）。结论Ｐ１６蛋白表达缺失与肺癌的发生有关，且随着分化程度的下降表达缺失增加。     

抑癌基因P16在肺鳞癌和肺腺癌中的表达及临床意义

目的 探讨p16基因产物在肺鳞癌和肺腺癌中的表达及其意义。方法 本组56例原发性非小细胞肺癌，其中鳞癌37例，腺癌19例。用免疫组织化学PCR法检测患者肺癌新鲜标本p16蛋白表达水平。结果 56例肺癌标本中p16蛋白阳性表达率为58.9%（33／56），伴有淋巴结转移者其阳性表达率41.4%（12／29）显著低于无淋巴结转移者（P16阳性表达率为77.8%（21／27），P＜0.01）。P16蛋白阴性表达者的1年、3年生存率分别为59.7%、44.1%，显著低于p16蛋白阳性表达者85.2%、71.8%。结论 p16蛋白表达与肺鳞癌和肺腺癌的组织类型，淋巴结转移及预后有关。p16蛋白状态可作为判断肺癌预后的指标之一。     

肺鳞癌、腺癌中Survivin表达及其与VEGF和P53表达的相关性研究

目的探讨肺鳞癌、腺癌组织中survivin表达、临床意义及其与VEGF、P53表达的相关性。方法采用免疫组织化学（Envision二步法）检测survivin、VEGF和P53在116例肺鳞癌、腺癌组织及15例肺良性病变组织中的表达情况。结果 survivin、VEGF、P53的阳性率分别为62.1%（72/116）、72.4%（84/116）、55.2%（64/116）,显著高于肺良性病变组织的survivin表达与肺鳞癌、腺癌的低分化（P〈0.05）、淋巴结转移呈正相关（P〈0.05）,与患者预后负相关（P〈0.05）;VEGF和p53的表达与肺癌组织的分化程度、TNM分期及淋巴结转移均有关（P〈0.05）;并且Survivin表达与VEGF、P53表达呈正相关（P〈0.05）。结论 Survivin的表达与肺鳞癌、腺癌的低分化、淋巴结转移正相关;过度表达提示预后不良;Survivin有望成为肺癌诊断和基因治疗的新靶点;survivin、VEGF和P53三者的协同表达可能是促进肺癌恶性进展的重要因素。     

Expression of the multidrug resistance-associated protein 1 (MRP1) and the lung resistance-related protein (LRP) in human lung cancer

Fifty lung cancer samples (41 non-small cell lung cancer-NSCLC and 9 small cell lung cancer-SCLC) were immunohistochemically analyzed for lung resistance-related protein (LRP) and multidrug resistance-associated protein 1 (MRP1) expressions which were then correlated with histopathological subtype of the tumor. To detect these proteins, monoclonal antibodies LRP-56 and MRPm6 were used. NSCLC samples were divided into two groups, adenocarcinomas (17 samples) and squamous cell carcinomas (24 samples). Four categories of LRP and MRP1 quantity were distinguished: +++ = high level--90--100% of positive cells, ++ = lower level--10--90% of positive cells, + = low level--up to 10% of positive cells, - = negative cells--0% of positive cells. Within the NSCLC group the most samples (36/41) had the similar level of LRP and MRP1. Significantly higher expression of both proteins was observed in the adenocarcinomas in comparison with squamous cell carcinomas. The lowest positive staining for LRP and MRP1 proteins has been found in SCLC. It is suggested that our finding can confirm the overall empirical clinical knowledge about much higher chemosensitivity of untreated SCLC comparing to NSCLC.     

Loss of heterozygosity (LOH) in non-small cell lung cancer: difference between adenocarcinoma and squamous cell carcinoma

BACKGROUND: In non-small cell lung cancer, a loss of heterozygosity (LOH) is frequently observed; however, few studies have investigated the differences in the LOH status between adenocarcinoma and squamous cell carcinoma. PATIENTS AND METHODS: In a consecutive series of 49 patients with adenocarcinomas and 22 patients with squamous cell carcinomas, the LOH in tumors was analyzed using polymerase chain reaction employing 5 fluorescence-labeled dinucleotide markers (D2S123, D5S107, D10S197, D11SS904, D13S175) and an autosequencer. RESULTS: LOH was more frequently observed in squamous cell carcinoma (20 of 22, 90%) than in adenocarcinomas (33 of 49, 67%) (P=0.0348), and the number of LOH per patient was also higher in the patients with squamous cell carcinoma (2.2+/-1.4) than in those with adenocarcinoma (1.5+/-1.2, P=0.037). In adenocarcinomas, the number of LOH per patients correlated significantly with the pack-year index, whereas the pathological stage significantly affected the number of LOH in squamous cell carcinomas. CONCLUSION: The presence of LOH is relatively uncommon in adenocarcinoma of the lung; however, the incidence of LOH tends to be associated with the smoking status.     

mdr1基因的表达和肺癌多药耐药的关系

目的进一步研究ｍｄｒ１基因的表达与原发性肺癌多药耐药的关系。方法应用逆转录多聚酶链式反应（ＲＴ－ＰＣＲ）方法对４３例未治、５例化疗后的原发性肺癌和３３例癌旁正常肺组织ｍｄｒ１基因的表达进行分析。结果４８例癌标本中有１５例被观察到ｍｄｒ１基因的过度表达，主要分布在非小细胞肺癌（ＮＳＣＬＣ）中，仅１例化疗后标本ｍｄｒ１阳性。ｍｄｒ１基因的过度表达与肿瘤大小，淋巴结转移和病期无明显相关性。随访一年后发现，过度表达ｍｄｒ１基因的病例，其复发率高于无过度表达者。结论在未治的原发性肺癌尤其是ＮＳＣＬＣ中可检测到ｍｄｒ１基因的过度表达，并且可能是提示不良预后的指标。     

Frequent loss of the short arm of chromosome 9 in resected non-small-cell lung cancers from Japanese patients and its association with squamous cell carcinoma

We analyzed 87 Japanese non-small-cell lung carcinomas (NSCLC), including 30 squamous cell, 51 adenocarcinomas and 6 large-cell carcinomas for loss of heterozygosity (LOH) on the short arm of chromosome 9, and we correlated our findings with clinicopathological features. We used four polymorphic microsatellite markers on 9p (interferon A gene, D9S171, D9S126, and D9S169), which flank the critical region (9p21-22) involved in lung cancer. We observed alterations of DNA sequences at 9p in NSCLC (27 of 82 informative cases or 33%). Concordance among the four markers was high (87%), indicating that the deletions often were relatively large. The 27 genetic alterations observed on 9p include 26 examples of LOH, 1 homozygous deletion, and 1 case with LOH and evidence of microsatellite alteration characterized by shift in band mobility. We noted a high frequency of LOH at 9p especially in, squamous cell carcinoma (17 of 29 informative cases or 59%) and in poorly differentiated NSCLC (12 of 23 informative cases or 52%). There was no correlation between LOH at 9p and the other clinical parameters, including survival, gender, tumor size and the presence of regional or distant metastases. In contrast to other reports we found only rare instances of homozygous deletions (1%) and microsatellite alteration showed as a mobility shift (1%). Our findings demonstrate that LOH at the short arm of chromosome 9 is correlated with squamous cell and poorly differentiated carcinomas in Japanese patients with NSCLC.Abbreviations SCLC small-cell lung cancer - NSCLC non-small-cell lung cancer - LOH loss of heterozygosity - PCR polymerase chain reaction - (CA) _n cytosine adenine - n number of repeats - IFNA interferon A gene     

舌鳞癌组织中Cyclin D1、VEGF的表达变化及其相关性

目的观察Cyclin D1、血管内皮生长因子（VEGF）在舌鳞癌组织中的表达及意义。方法采用免疫组化SP法检测45例舌鳞癌组织及正常舌黏膜组织中Cyclin D1、VECF的表达变化。结果舌鳞癌组织中Cyclin D1、VECF的阳性表达率分别为62．2％、71．1％,均高于正常舌黏膜（P均〈0．01）;Cyclin D1表达与舌鳞癌的组织分级、临床分期有关（P〈0．05）,VEGF表达与舌鳞癌的临床分期、淋巴结转移有关（P〈0．05）;Cyclin D1与VECF表达呈正相关（r=0．515,P〈0．01）。结论Cyclin D1和VEGF在舌鳞癌组织中呈过表达,二者表达呈正相关。联合检测Cyclin D1和VEGF可以做为判断舌鳞癌生物学行为和指导临床治疗的指标。     

Infrequent ERBB2 mutations in Chinese patients with non-small cell lung cancer

ERBB2 mutations have been reported to occur in a subset of patients with lung adenocarcinomas or lung squamous cell carcinomas for some ethnicities, but it is unclear for Chinese patients with lung squamous cell carcinomas up to now. We retrospectively evaluated the status of ERBB2 mutations in a large cross-sectional cohort of 212 Chinese patients with non-small cell lung cancer (NSCLC) diagnosed in several hospitals from southern China during a time period of 1.5 years by polymerase chain reaction (PCR)-based direct sequencing and PCR-single strand conformation polymorphism (PCR-SSCP) analysis. ERBB2 mutation was found in 1 of 49 lung adenocarcinomas (2.0%) and none in lung squamous cell carcinomas and lung adenosquamous carcinomas. It implies the occurrence of ERBB2 mutations is infrequent in Chinese patients with NSCLC, especially in lung squamous cell carcinomas.     

非小细胞肺癌EBUS-TBNA标本中TTF-1、CK7、CK5/6和p63的表达及其意义

目的：探讨在非小细胞肺癌支气管内超声引导针吸活检(EBUS-TBNA)标本中TTF-1、CK7、CK5/6和 p63的表达及其意义。方法采用免疫组化 SP 法检测64例非小细胞肺癌患者EBUS-TBNA标本的TTF-1、CK7、CK5/6和 p63的表达情况。结果 TTF-1和 CK7在肺腺癌患者EBUS-TBNA标本中的表达阳性率分别为75.00%和100.00%,明显高于肺鳞癌(χ2值分别为16.94、32.00,P值均<0.05);CK5/6和 p63在肺鳞癌患者 EBUS-TBNA标本中的表达阳性率分别为91.67%和75.00%,明显高于肺腺癌(χ2值分别为11.45、4.80,P 值均<0.05)。结论检测非小细胞肺癌EBUS-TBNA标本的TTF-1、CK7、CK5/6和 p63对鉴别肺鳞癌和腺癌有重要意义。