胰腺癌组织中SERPINB5的表达及意义

目的探讨SERPINB5在胰腺癌中的表达及其临床意义。方法利用组织芯片技术及免疫组化SP法检测SERPINB5在胰腺癌、癌旁组织与慢性胰腺炎组织中的表达,分析它与胰腺癌的临床病理指标间的相关性。结果 47例胰腺癌组织中SERPINB5的阳性表达率为85.11%(40/47),而16例癌旁及慢性胰腺炎组织中SERPINB5的阳性表达率为25%(4/16),两者比较差异有统计学意义(P<0.05);SERPINB5在胰腺癌组织中的表达与患者性别、年龄、肿瘤部位、肿瘤组织学类型及神经浸润均无关(P均>0.05)。结论 SERPINB5阳性表达与胰腺癌相关,提示SERPINB5可能在胰腺癌的发生、发展中起重要作用。     

存活素和尿激酶型纤溶酶原激活剂在人胰腺癌组织中的表达意义及相关性分析

目的分析存活素(Survivin)和尿激酶型纤溶酶原激活剂(u PA)在人胰腺癌中的表达及两者之间的相关性。方法采用免疫组化PV法检测原发性胰腺癌组织(63例)及癌旁非肿瘤胰腺组织(11例)中Survivin和u PA的表达,分析两者间表达的相关性及与胰腺癌临床病理特征的关系。结果 63例胰腺癌组织中Survivin和u PA阳性率分别为69.8%(44/63)、65.1%(41/63),11例癌旁非肿瘤胰腺组织中均无表达,Survivin和u PA表达呈正相关(r=0.389,P0.050),两者与胰腺癌TNM分期、分化程度及淋巴结转移均有关(P均0.05)。结论 Survivin和u PA在胰腺癌组织中的表达呈正相关,两者表达上调在胰腺癌的发生、发展、侵袭和转移中起重要作用。     

次级淋巴组织趋化因子及其受体CCR7在胰腺癌中的表达及临床意义

目的 研究胰腺癌中次级淋巴组织趋化因子(SLC)及其受体CCR7的表达情况,探讨其与胰腺癌临床病理关系.方法 应用免疫组化、RT-PCR和实时荧光定量PCR技术检测30例胰腺癌组织、癌旁组织、正常胰腺组织和胰周淋巴结组织中SLC和CCR7的表达情况.结果 SLC蛋白在胰腺癌组织中呈低表达状态、在癌旁组织和胰周淋巴结均呈中等表达状态、在正常胰腺组织中高表达,阳性率分别为16.7%(5/30)、43.3%(13/30)、46.6%(14/30)和76.7%(23/30).RT-PCR和实时荧光定量PCR也证实SIC mRNA表达与SIC蛋白相同.CCR7蛋白在胰腺癌组织、癌旁组织和胰周淋巴结均呈高表达状态、在正常胰腺组织中呈低表达状态,阳性率分别为76.7%(23/30)、66.7%(23/30)、70.0%(/30)和30.0%;同时还发现CCR7蛋白在胰腺静脉平滑肌和淋巴结外脂肪组织也有阳性表达情况.RT-PCR和实时荧光定量PCR结果 也证实CCR7 mRNA表达与CCR7蛋白相同.结论 SLC在胰腺癌进展和淋巴结转移过程中起双重作用,既发挥抗肿瘤作用,又通过趋化CCR7表达阳性的肿瘤细胞促进胰腺癌的淋巴结转移.CCR7与胰腺癌淋巴结转移和TNM分期密切相关,并可能参与胰腺癌的淋巴管生成和淋巴结转移的调控.     

肿瘤标志物mesothelin在胰腺癌组织的表达及其临床意义

研究胰腺癌组织mesothelin的表达及其与临床肿瘤指标的关系.收集43例手术切除的胰腺癌及39例癌旁胰腺组织石蜡标本,利用EnVision免疫组化法分别检测癌组织和癌旁胰腺组织mesothelin的表达情况.结果显示,43例胰腺癌组织中mesothelin阳性表达32例(74.4%),39例癌旁胰腺组织中无阳性表达病例;mesothelin阳性率与肿瘤分化程度有关(P＜0.005),与肿瘤的大小、淋巴及远处转移无关(P＞0.05).结论:mesothelin在胰腺癌组织中有较高的阳性表达率,检测其表达有助于胰腺癌的诊断,并可作为判断胰腺癌恶性程度的重要指标.     

神经源性分化蛋白在胰腺癌中的表达和意义

目的 探讨神经源性分化蛋白(NeuroD)在胰腺外分泌癌中的表达及其意义.方法 应用组织芯片和免疫组织化学EnVision二步法研究NeuroD、增殖细胞核抗原(PCNA)、p53在127例胰腺外分泌癌中的表达情况,并在光镜下观察胰腺癌神经组织浸润、神经周围淋巴细胞套、癌旁慢性胰腺炎、胰周淋巴结转移情况.分析NeuroD的表达与上述其他指标及性别、年龄、肿瘤部位、肿瘤组织学类型及分化程度等的关系.结果 NeuroD、PCNA和p53蛋白在胰腺癌组织中的阳性率分别为64.6％(82/127)、57.5％ (73/127)和59.1％ (75/127),与菲癌组织[分别为10.5％ (8/76)、9.2％(7/76)和9.2％(7/76)]相比,差异有统计学意义(P＜0.01).NeuroD蛋白的表达与PCNA、p53蛋白的表达和胰腺癌肿瘤神经浸润之间有统计学相关性(P＜0.05),而与性别、年龄、肿瘤部位、肿瘤组织学类型及分化程度、癌旁慢性胰腺炎、神经周围淋巴细胞套和淋巴结转移均等无统计学相关性(P＞0.05).结论 NeuroD蛋白在胰腺癌中呈高表达,可能参与了胰腺癌的发生和进展,并且与胰腺癌的增殖、p53信号通路和肿瘤神经浸润之间密切相关.     

胃癌患者外周血及癌组织中上皮细胞黏附分子和存活素的表达及意义

目的:观察胃癌患者外周血及癌组织中上皮细胞黏附分子(EP-CAM)及存活素的表达水平及探讨其在胃癌发生及发展中的临床意义。方法:采用RT-PCR检测正常对照组和胃癌组患者外周血EP-CAM及存活素mRNA水平;免疫组化法观察癌旁上皮组织和胃癌组织中EP-CAM及存活素蛋白表达。结果:正常对照组外周血EP-CAMmRNA相对表达水平为0.05±0.01,存活素mRNA相对表达水平为0.02±0.01,胃癌组EP-CAM相对表达水平为0.82±0.02,存活素相对表达水平为0.61±0.04,两者均显著高于正常对照组(P<0.01);癌旁上皮组织中EP-CAMMOD为0.005±0.001,存活素MOD为0.004±0.001,胃癌细胞EP-CAM的MOD为0.309±0.054,存活素MOD为0.331±0.066,两者均显著高于癌旁对照组织(P<0.01)。结论:EP-CAM及存活素mRNA和蛋白高表达可能参与了胃癌的发生发展。     

胰腺癌组织中干细胞转录因子Sox2及Oct4的表达及意义

目的探讨干细胞转录因子Sox2及Oct4在胰腺癌组织中的表达及其临床意义。方法选择中日友好医院病理科存档的配对胰腺癌及其对应癌旁组织石蜡标本各67例,采用免疫组化SP法检测胰腺癌及其癌旁组织中Sox2及Oct4蛋白的表达,并分析胰腺癌组织中Sox2蛋白表达与临床病理特征及Oct4表达的相关性。采用Kaplan-Meier法绘制生存曲线,比较Sox2及Oct4蛋白表达对患者生存的影响。结果 Sox2在胰腺癌组织中阳性34例,阳性率为50.75%,而在癌旁组织中均为阴性,胰腺癌组织中Sox2阳性率显著高于癌旁组织(P0.01)。Oct4在胰腺癌组织中阳性32例,阳性率为47.76%,而在癌旁组织中均为阴性,胰腺癌组织中Sox2阳性率显著高于癌旁组织(P0.01)。胰腺癌组织中Sox2及Oct4表达与肿瘤分化程度、淋巴结转移、AJCC分期相关(P0.05),与患者性别、年龄、肿瘤部位、肿瘤直径、浸润深度、肝转移均无关(P0.05)。Sox2与Oct4表达呈正相关(P0.05)。胰腺癌组织中Sox2及Oct4阴性患者的术后生存情况显著优于阳性患者(P0.05)。结论干细胞转录因子Sox2及Oct4蛋白表达与胰腺癌疾病的发生、发展及患者预后有关,且Sox2与Oct4表达密切相关,Sox2及Oct4有望成为胰腺癌新的肿瘤标志物以及预后监测指标。     

ILK在胰腺癌中的表达及临床病理意义

目的研究整合素连接激酶(ILK)在胰腺癌中的表达情况及其与临床病理特征的关系。方法利用免疫组织化学方法和Western Blot方法检测61例胰腺癌标本,26例癌旁组织,4例正常胰腺组织中ILK蛋白的表达情况,并统计分析其表达率与临床病理学特征的相关性。结果免疫组织化学染色示ILK蛋白定位于细胞浆,其表达率为65.6%,其中7例Ⅲ期胰腺癌中有6例ILK染色强度均呈(+++);26例癌旁组织中有3例阳性表达,表达率11.5%;4例正常胰腺组织未见ILK的表达,胰腺癌组织的ILK表达明显高于可配对癌旁组织(P0.05)及正常胰腺组织(P0.01)。Western Blot检测发现胰腺癌组织ILK蛋白的表达水平明显高于癌旁组织(P0.01)。结论 ILK高表达与胰腺癌患者病理类型中的分化程度无关,而与肿瘤的淋巴结转移、临床分期密切相关。     

非小细胞肺癌组织中TRIM59、p53表达与临床病理特征及预后的相关性分析

目的 分析非小细胞肺癌(NSCLC)组织中三重基序蛋白(TRIM)59、p53表达与患者临床病理特征及预后的关系。方法 选取我院73例NSCLC患者的癌组织及癌旁组织,免疫组织化学法检测患者NSCLC组织及癌旁组织中TRIM59及p53蛋白的表达;qRT-PCR检测TRIM59及p53 mRNA表达。Pearson检验分析NSCLC组织中TRIM59 mRNA与p53 mRNA表达的相关性;采用TCGA数据库分析TRIM59及p53蛋白与NSCLC患者预后的关系;Kaplan-Meier法分析TRIM59、p53蛋白与NSCLC患者预后的关系;COX回归分析影响NSCLC患者预后的危险因素。结果 NSCLC组织中TRIM59及p53蛋白阳性表达率显著高于癌旁组织(74.0%vs.9.6%,65.8%vs.5.5%,P<0.05),TRIM59 mRNA、p53 mRNA表达水平显著高于癌旁组织[(2.17±0.62)vs.(1.00±0.24)、(1.85±0.49)vs.(1.00±0.26),P<0.05]。NSCLC组织中TRIM59及p53蛋白阳性表达与患者TNM分...     

Glypican-3在多种肿瘤中的表达

目的:研究Glypican-3在多种肿瘤中的表达及意义.方法:免疫组化方法检测Glypiean-3在461例多种肿瘤及部分正常组织中的表达.结果:多种肿瘤中:Glypican-3在肝癌中阳性率为74.4%(119/160),大肠癌中Glypican-3阳性率为66.0%(132/200),Glypican-3在肝癌及大肠癌组织中表达明显高于癌旁组织(P<0.05);Glypican-3在子宫内膜癌(3/16),肺癌(3/32),乳腺癌(1/15),卵巢癌(1/11),胰腺癌(0/15),食管癌(1/12)等肿瘤中表达较低,Glypican-3在癌组织中的表达与癌旁组织无统计学意义.在正常组织如肾,胎盘,乳腺当中Glypican-3表达为阳性,其他多种正常组织中表达均为阴性.结论:Glypican-3在肝癌、大肠癌、肺癌等中均有不同程度表达,且表达意义不尽相同,Glypican-3可能在多种肿瘤发生、发展中起重要作用.     

Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma.

The non-neoplastic pancreatic parenchyma adjacent to infiltrating ductal adenocarcinoma demonstrates inflammation, fibrosis, acinar cell loss and small duct-like metaplasia of acinar cells. Similar morphologic changes are also observed in the setting of chronic pancreatitis. In addition, peritumoral acini have been shown to have alterations in gene expression even in the absence of morphological changes. To better understand the pancreatic acinar responses to infiltrating pancreatic ductal adenocarcinoma, we characterized gene expression patterns of pancreatic acinar tissue adjacent to infiltrating pancreatic ductal adenocarcinomas and compared them to gene expression patterns of acinar tissue affected by chronic pancreatitis as well as to those of normal pancreatic acini. Fresh-frozen pancreatic acinar tissue was microdissected from nine patients (three with pancreatic cancer, three with chronic pancreatitis, three with normal pancreata) using laser capture microdissection, and extracted RNA from each microdissection was subjected to two rounds of linear amplification and hybridized to oligonucleotide microarrays. Gene expression patterns were confirmed using quantitative RT-PCR and/or immunohistochemistry. A total of 20 genes was found to be overexpressed in peritumoral acinar tissue compared to normal acinar tissue and to acini affected by chronic pancreatitis. These 20 genes included pancreatitis-associated protein (HIP/PAP), a gene known to be overexpressed in acini adjacent to infiltrating pancreatic cancer, and the gene cartilage glycoprotein-39 (HC gp-39 or TKL-40). Serum HC gp-39 protein levels were significantly higher in patients with pancreatic cancer and in those with chronic pancreatitis than in controls without pancreatic disease. There was no significant difference in the levels of serum HC gp-39 in patients with pancreatic cancer and those with chronic pancreatitis. Our results demonstrate some of the molecular alterations in acinar cells that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma and reveal that such alterations can provide a rich source of markers of pancreatic cancer.     

胰腺导管腺癌中HER2/neu和拓扑异构酶Ⅱα基因的变化及相关性分析

目的探讨胰腺导管腺癌（简称胰腺癌）中HER2／neu和拓扑异构酶ⅡαTOP2A）基因的变化及其意义。方法应用免疫组织化学（EnVision法）和多色荧光原位杂交技术,检测26例中国人胰腺导管腺癌及癌旁胰腺组织、10例慢性胰腺炎组织、10例正常胰腺组织中TOP2A和HER2／neu蛋白表达及基因状态的变化,分析蛋白表达与基因扩增间的关系,以及TOP2A和HER2／neu基因改变的相关性,并探讨二者与胰腺癌临床病理改变之间的关系。结果26例胰腺癌组织中免疫组织化学显示TOP2A阳性表达指数从0．5％至70％,12例（46．2％）胰腺癌组织HER2／neu蛋白阳性表达。荧光原位杂交结果显示TOP2A和HER2／neu基因扩增的胰腺癌各10例（38．5％）,其中9例为TOP2A和HER2／neu共同扩增,癌旁胰腺组织、慢性胰腺炎及正常胰腺组织均未检测到TOP2A和HER2／neu蛋白表达及基因扩增。TOP2A和HER2／neu蛋白表达水平与基因扩增无显著相关性（P〉0．05）。TOP2A和HER2／neu基因扩增具有显著的相关性（P〈0．01）。结论胰腺癌中TOP2A和HER2／neu的蛋白表达与基因扩增无相关性;TOP2A和HER2／neu基因的共同扩增可能在胰腺癌发生发展中起重要作用,联合检测TOP2A和HER2／neu基因状态对于胰腺癌的靶向治疗可能具有一定的指导意义。     

Maspin is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: a tissue microarray based study.

Maspin, a member of the serpin family of serine protease inhibitors, has been shown to limit invasion and metastases in breast and prostate carcinomas. Maspin gene expression is up-regulated in pancreatic cancer, but not in normal pancreatic tissue. Maspin expression has been documented using immunohistochemical studies in pancreatic adenocarcinoma and high-grade intraductal dysplasia. We studied pancreatic ductal adenocarcinomas and chronic pancreatitis utilizing tissue microarray technology to determine the utility of maspin in differentiating these lesions. Immunohistochemistry was performed on tissue microarrays made from 72 cases of pancreatic ductal adenocarcinoma and 24 cases of chronic pancreatitis. Carcinomas were graded as well, moderately, or poorly differentiated using the WHO criteria. The primary antibody used was monoclonal antimaspin antibody (clone G167-70, 1:800, PharMingen, San Diego, CA). Nuclear and/or cytoplasmic staining for maspin was qualitatively scored from 1 + to 3 + based on intensity. Cases were considered positive if one or more cores demonstrated staining. Cases of chronic pancreatitis showed focal, weak (1 + to 2 +) staining within occasional benign ductal epithelial cells in 29% of cases (7/24). Diffuse and intense (3 +) staining was present in ducts with squamous metaplasia (3 cases). The majority of ducts showed no staining. Ductal adenocarcinomas showed diffuse staining in 91% (66/72) of cases with generally more intense staining than cases of chronic pancreatitis. Maspin may be helpful in differentiating ductal adenocarcinoma from chronic pancreatitis, once squamous metaplasia is ruled out.     

Differential MUC 1 expression in normal and neoplastic human pancreatic tissue. An immunohistochemical study of 60 samples.

Neoplastic transformation of epithelial cell sis commonly associated with altered synthesis of mucin glycoproteins. Few studies have been performed on the correlation between MUC 1 expression and pancreatic carcinoma using immunohistochemical methods. We compared the patterns of MUC 1 expression in normal pancreatic tissue, in pancreatic carcinoma, and in chronic pancreatitis. Immunohistochemical studies were performed using 3 monoclonal anti-MUC 1 antibodies (12C10, 1G5, and H23) on surgical specimens and on fine-needle aspiration biopsy specimens. In the neoplastic cells from adenocarcinomas, high levels of cytoplasmic MUC 1 expression were observed, with some membrane staining. No such cytoplasmic expression was observed in normal tissue, tissue from chronic pancreatitis, or benign neoplastic tissue. These data show conspicuous quantitative and qualitative differences between the patterns of MUC 1 expression observed in nonmalignant vs malignant pancreatic tissue and may be useful in the histologic diagnosis of adenocarcinoma in biopsy samples.     

Survivin蛋白表达与胃癌发生发展的关系及意义--组织芯片技术研究

目的探讨凋亡抑制基因Survivin编码蛋白表达与胃癌发生发展的关系及其相关分子病理学机制。方法采用组织芯片仪(M icroarrayer,Beecher Instrum ents,USA)构建含98例胃癌及其癌前病变的直径1.0 mm的225个微组织阵列芯片,免疫组织化学方法检测分析survivin蛋白表达情况。结果胃癌及其癌前病变组织芯片蜡块组织阵列排列整齐,常规切片组织形态良好。凋亡抑制基因survivin编码蛋白在胃癌组织中的表达阳性率显著高于正常胃黏膜、肠上皮化生、不典型增生组织中的表达(P<0.01),胃癌转移组survivin蛋白表达阳性率显著高于无转移组(P<0.05)。Survivin蛋白表达与胃癌病理分期、组织学类型和大体类型没有相关性(P>0.05)。结论组织芯片技术在人胃癌早期诊断中具有其他组织病理学技术不可替代的高效、省时、低消耗的优点。Survivin在胃黏膜癌变过程中被激活而参与胃癌的发生和发展,可作为一个较为理想的肿瘤标志物用于胃癌的早期诊断和转移的预警。     

肿瘤-睾丸抗原SSX、NY-ESO-1、MAGE-A1在胰腺癌中的表达及其生物学意义

目的 检测肿瘤-睾丸抗原(CTA)SSX、NY-ESO-1、MAGE-A1在正常胰腺组织、慢性胰腺炎以及胰腺癌中的表达情况,寻找胰腺肿瘤中高表达的CTA.方法 应用免疫组织化学SP法检测8例正常胰腺组织、15例慢性胰腺炎组织、52例胰腺癌组织中SSX、NY-ESO-1、MAGE-A1的表达.Western blotting检测52例胰腺癌组织中SSX、NY-ESO-1、MAGE-A1的表达.结果 正常胰腺组织、慢性胰腺炎中SSX、MAGE-A1和NY-ESO-1均不表达,SSX、NY-ESO-1、MAGE-A1在52例胰腺癌的阳性表达率分别为48.08%(25/52)、7.69%(4/52)、5.77%(3/52);经相关分析,SSX、NY-ESO-1和MAGE-1的阳性表达与患者的年龄、性别、病变部位、分化程度均未见明显相关关系(P＞0.05); SSX的表达与肿瘤的浸润转移呈负相关(r=-0.306,P=0.028); 52例胰腺癌病例中55.77%(29/52)有1种以上的CTA表达.结论 不同种类的CTA在胰腺癌中的表达存在显著差异,SSX的阳性表达率最高;胰腺癌中SSX的高表达与肿瘤的转移呈明显的负相关关系;CTA在胰腺癌中的表达呈现簇生现象.     

Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis

Mesothelin, a cell surface glycoprotein present on normal mesothelial cells, has been reported to be expressed in pancreatic adenocarcinomas. We conducted this study to fully characterize mesothelin expression in surgically resected, formalin-fixed, paraffin-embedded tissue specimens of 18 pancreatic adenocarcinomas, 9 adenocarcinomas of the ampulla of Vater, 12 adenocarcinomas of the common bile duct, and 17 cases of chronic pancreatitis. Mesothelin immunostaining was performed using the antimesothelin monoclonal antibody 5B2. All 18 cases (100%) of pancreatic adenocarcinomas showed mesothelin expression, as did 8 (89%) of 9 cases of ampullar adenocarcinoma and all 12 cases (100%) of common bile duct adenocarcinoma. In all cases of pancreaticobiliary adenocarcinoma, the adjacent normal pancreas did not stain for mesothelin. Of 17 specimens of chronic pancreatitis, 16 were negative for mesothelin expression, and 1 case showed weak mesothelin staining of fewer than 5% of normal pancreatic ducts. Our results demonstrated mesothelin expression in the majority of pancreaticobiliary adenocarcinomas and no expression in normal pancreatic tissues and in chronic pancreatitis.     

RASA1在胰腺癌中的异常表达及其临床意义

目的: 探讨Ras p21蛋白活化子1(Ras p21 protein activator 1,RASA1)在胰腺癌中的表达状况及可能作用。方法: 以qRT-PCR检测胰腺癌细胞(Capan-2、CFPAC-1、BxPC-3)和胰腺导管上皮细胞(H6C7)中RASA1 mRNA表达水平的差异,以Western blotting检测上述细胞之间RASA1蛋白表达水平的差异;以免疫组化检测RASA1蛋白在胰腺癌及胰腺良性病变(慢性胰腺炎、胰腺囊肿)中的表达差异,并观察其表达水平与胰腺癌各临床病理因素之间的联系。结果: 各胰腺癌细胞株中RASA1 mRNA和蛋白表达水平均低于胰腺导管上皮细胞(P<0.05)。肿瘤组织RASA1蛋白表达水平显著低于良性病变组织(P<0.05);侵犯周边器官的肿瘤组织中RASA1表达显著低于局限于胰腺内的组织(P<0.05);Ⅰ期胰腺癌组织RASA1的表达则显著高于Ⅱ、Ⅲ期的癌组织(P<0.05);但RASA1表达与胰腺癌的远处转移关系尚不明确。结论: RASA1作为抑癌蛋白可能在胰腺癌的发生发展中发挥重要作用。