胃癌组织中C-erbB-2和ki67的表达及临床意义

探讨C-erbB-2和ki67蛋白在胃癌组织中的表达情况与胃癌分化程度、浸润深度、淋巴结转移和脉管浸润的关系。采用免疫组织化学SP法分别观察87例胃癌患者组织c-erbB-2和ki67基因蛋白表达。C-erbB-2的阳性率为49.4%(43/87);在肠型中的阳性率为79.2%,在弥漫型中的阳性率为38.1%(P0.05);在有浆膜浸润中的阳性率为64.9%,在无浆膜浸润中的阳性率为20.0%(P0.05)。ki67在胃癌组织中的阳性率为67.9%(59/87);在肠型中的阳性率为45.8%,在弥漫型中的阳性率为76.2%(P0.05);在有浆膜浸润中的阳性率为77.2%,在无浆膜浸润中的阳性率为20.0%(P0.05);ki67在有淋巴结转移组中阳性表达率为73.0%,在无淋巴结转移组中阳性表达率为54.2%(P0.05);C-erbB-2和ki67在脉管浸润表达阳性率、C-erbB-2表达阳性率与有无淋巴结转移均无显著差异(P0.05)。结果表明,C-erbB-2和ki67蛋白与胃癌组织的分化程度、浸润深度关系密切,ki67与胃癌的淋巴结转移关系密切,C-erbB-2和ki67与胃癌有关脉管浸润及C-erbB-2与胃癌的淋巴结转移均无显著相关性。     

ki67和cyclin D1在肾癌组织中的表达及其临床意义

目的:探讨ki67和cyclin D1在肾细胞癌(RCC)组织中的表达及意义。方法:利用免疫组化方法检测ki67和cyclin D1在50例RCC组织中的表达情况。50例的病理分级G111例,G230例,G39例;TNM分期Ⅰ期24例,Ⅱ期16例,Ⅲ期5例,Ⅳ期5例。结果:RCC组织中ki67标记指数为(14.0±10.95)%,cyclin D1的阳性率为80%;ki67在RCC病理分级G1与G3,G2与G3之间表达差异显著,在Ⅰ期与Ⅲ期、Ⅳ期之间表达差异显著,Ⅱ期与Ⅲ期、Ⅳ期之间表达亦差异显著,ki67和cyclinD1在RCC及正常肾组织中的表达差异有统计学意义(均P<0.05)。结论:ki67和cyclinD1在RCC组织中存在着高表达,RCC组织中ki67标记指数随着病理分级和临床分期的增高而增高,与肿瘤的生物学行为有一定关系。     

胃癌组织中Ki-67和c—erbB-2的表达及意义

目的探讨Ki-67和c-erbB-2在胃癌组织中的表达及其临床意义。方法对95例胃癌组织石腊切片进行免疫组织化学染色．分析Ki-67和c-erbB-2在胃癌组织中的表达及其与病理特征的关系。结果95例胃癌组织中Ki-67阳性表达率为84．2％．其表达与胃癌的分化程度显著相关（P〈0．05）,而与胃癌大体分型、浸润深度及淋巴结转移无明显相关性（P〉0．05）。c—erbB-2阳性表达率为66.3％．其表达与胃癌组织的分化程度、浸润深度及淋巴结转移相关（P〈0．05）,而与胃癌大体分型无明显相关（P〉0．05）。胃癌组织中Ki．67表达与c—erbB-2的表达存在显著正相关（P〈0．05）。结论Ki-67和c-erbB-2在胃癌组织中均有较高表达．可在一定程度上反映细胞增殖活性和细胞分化水平。     

CDX-2和COX-2在胃癌中的表达及临床意义

目的:探讨尾型同盒转录子-2(CDX-2)和环氧合酶-2(COX-2)在胃癌组织中的表达及临床意义.方法:采用免疫组织化学EnVision两步法检测CDX-2和COX-2在75例胃癌组织和30例癌旁组织中的表达,分析其与胃癌临床病理特征的关系以及两者的相关性.结果:CDX-2和COX-2在胃癌组织中的阳性表达率分别为53.3%和65.3%,高癌旁组织30.0%(P<0.05)和33.3%(P<0.01).在胃癌组织中表达呈明显负相关(P<0.01).结论:CDX-2和COX-2均参与了胃癌的发生、发展,CDX-2主要在肠型胃癌中表达,CDX-2的低表达与COX-2的高表达有助预测胃癌病情进展的情况.     

Bcl基因与Ki—67抗原在胃癌组织中表达的研究

目的:探讨bcl-2基因和Ki-67抗原在胃癌中的表达及其可能的作用和意义.方法:用免疫组织化学LSAB法检测bCI-2和Ki-67在胃癌中的表达.结果:正常胃粘膜中bcl-2基本无表达.慢性萎缩性胃粘膜中可见基底部有bcl-2表达.7例胃癌bcl-2表达阳性,其中肠型胃癌阳性高于弥漫型.bcl-2的表达与胃癌的浸润深度和淋巴结转移无关.弥漫型胃癌的Ki-67表达显著高于肠型胃癌.Ki-67指数随浸润深度的增加而增高.有淋巴结转移的Ki-67指数显著高于无转移者.结论:bcl-2的表达可能对胃癌特别是肠型胃癌的发生有重要作用.Ki-67的表达与胃癌的发展及其预后的判断可能有意义.     

CDX2和PTEN蛋白表达与胃黏膜肠上皮化生关系的临床研究

目的：探讨CDX2和PTEN蛋白表达与胃黏膜肠上皮化生（简称肠化）的关系。方法：观察肠化的胃黏膜病理形态特点，应用免疫组织化学法检测23例单纯肠化、33例不典型肠化和44例胃癌中CDX2、PTEN蛋白的表达，分析其与单纯肠化、不典型肠化及胃癌的关系。结果：CDX2蛋白在单纯肠化、不典型肠化及胃癌中的阳性率分别为82．6％、51．5％和36.4％，胃癌组织中的阳性表达率显著低于单纯肠化组织（X^2=12．9470，P〈0．05），而与不典型肠化组织比较差异无统计学意义（X^2=2．7010，P〉0．05）。PTEN蛋白在单纯肠化、不典型肠化及胃癌组织中的阳性表达率分别为86．9％、75．8％和47．7％，胃癌与单纯肠化之间差异有统计学意义（X^2=9．7885，P〈0．05）。结论：CDX2蛋白异常表达参与了胃黏膜肠化及癌变的过程，PTEN蛋白对CDX2蛋白的表达可能起到一定的调节作用；不典型肠化与胃癌的关系密切，属癌前病变范畴。将肠化分类方法应用于不典型肠化患者的初步筛选，有望提高早期胃癌的检出率。     

Ki-67的表达与胃癌患者临床病理特征及预后的关系

目的探讨Ki-67在胃癌组织中的表达及其临床意义。方法采用免疫组化技术,检测326例胃腺癌组织及相应326例正常胃黏膜组织中Ki-67蛋白的表达情况。采用半定量RT-PCR实验检测,随机选取10例胃腺癌组织和相对应的正常胃黏膜组织中Ki-67mRNA的表达情况,应用χ2检验、Kaplan-Meier生存分析及COX回归分析与患者临床病理特征及预后的关系。结果胃癌组织中Ki-67蛋白和mRNA明显高于正常胃黏膜组织(P0.05)。Kaplan-Meier生存分析显示Ki-67蛋白表达与胃癌患者的预后密切相关(χ2=8.086,P=0.005),COX回归分析显示Ki-67为胃癌患者预后的独立因素(P=0.002)。结论 Ki-67的表达与胃癌预后密切相关,为胃癌患者预后的独立因素。     

SIRT-1及E-cadherin在胃癌组织中表达的相关研究

目的探讨沉默信息调节因子-1(silence signal regulating factor-1,SIRT-1)和上皮型钙黏附素(epithelial cadherin,E-cadherin)在胃癌组织中的表达及其临床意义。方法采用免疫组织化学SP方法检测SIRT-1和E-cadherin蛋白在胃癌组织及其相应的癌旁组织中的表达情况,采用Spearman方法分析SIRT-1与E-cadherin蛋白表达的相关性。结果 SIRT-1蛋白表达阳性率在胃癌组织中明显高于其相应的癌旁组织(χ~2=5.791,P=0.016),其在弥漫型胃癌组织中明显低于肠型胃癌组织(P0.05),而其阳性表达与胃癌患者的年龄、性别、肿瘤大小、肿瘤部位、分化程度、TNM分期及淋巴结转移均无关(P0.05)。E-cadherin蛋白表达阳性率在胃癌组织中明显低于其相应的癌旁组织(χ~2=10.868,P=0.001),其在弥漫型胃癌组织中明显高于肠型胃癌组织(P0.05);同样与胃癌患者的年龄、性别、肿瘤大小、肿瘤部位、分化程度、TNM分期及淋巴结转移均无关(P0.05)。SIRT-1与E-cadherin蛋白在胃癌组织中的表达呈负相关关系(r_s=–0.381,P=0.013)。结论胃癌组织中SIRT-1的表达增高可能通过下调E-cadherin表达从而促使肿瘤的发生和发展,SIRT-1及E-cadherin的表达变化可能参与了肠型胃癌的发生。     

Lgr5和Ki-67蛋白在胃癌组织中的表达研究

目的检测Lgr5和Ki-67蛋白在胃癌组织及其正常胃黏膜组织中的表达情况并分析其在胃癌发生及发展中的作用。方法采用SABC免疫组织化学方法测定69例胃癌患者的胃癌组织及其相应的正常胃黏膜组织中Lgr5和Ki-67蛋白表达情况并分析其与胃癌患者临床病理特征的关系。结果 Lgr5和Ki-67蛋白在胃癌组织中的表达阳性率均较其在正常胃黏膜组织中高[Lgr5蛋白:87.0%(60/69)比16.7%(5/30),χ2=45.81,P0.001;Ki-67蛋白:79.7%(55/69)比36.7%(11/30),χ2=17.43,P0.001]。Lgr5及Ki-67蛋白在低-未分化、N1～N3期及幽门螺杆菌(HP)感染阳性胃癌组织中的蛋白表达阳性率明显高于高-中分化、N0期及HP感染阴性患者(P0.050),Lgr5蛋白表达还与胃癌浸润深度有关(P0.050),而Ki-67蛋白表达与此无关(P0.050)。Lgr5及Ki-67蛋白表达与胃癌患者的性别和远处转移均无关(P0.050)。Lgr5蛋白表达与Ki-67蛋白表达呈明显的正相关关系(rs=0.340,P=0.004)。结论 Lgr5蛋白可能参与了肿瘤组织的局部浸润和淋巴结转移过程并与肿瘤恶性程度有关,Ki-67蛋白也可能参与了肿瘤淋巴结转移过程且也与肿瘤恶性程度有关,且此二者在肿瘤发生和发展中可能具有协同作用,同时HP感染可能与Lgr5和Ki-67蛋白协同参与了肿瘤发生、发展过程。     

p53和c-erbB-2与胃癌关系的研究进展

目的介绍近年来抑癌基因p53和癌基因c-erbB-2与胃癌关系的研究进展。方法收集近年来国内、外关于胃癌中p53和c-erbB-2的相关文献并进行综述。结果 p53基因突变和c-erbB-2的过表达是胃癌发生中的常见事件。p53突变与胃癌的发生部位及其侵袭性生物学行为有关;c-erbB-2的过表达可作为判断胃癌预后的独立参数。针对p53及c-erbB-2的基因靶向治疗药物也在不断研究中。结论深入研究p53与c-erbB-2基因在胃癌发生、发展中的作用,将有助于清楚地认识胃癌的生物学行为,并为胃癌的基因治疗提供理论依据。     

Experimental Barrett's esophagus and the origin of intestinal metaplasia

Many questions remain unanswered regarding the pathogenesis and the cell origin of Barrett's esophagus. Recent studies suggest that progenitor cell populations, which are presumed to reside at the basal layer in the squamous epithelium and at the esophageal glands duct epithelium, may differentiate into a glandular phenotype leading to the development of columnar epithelium in the distal esophagus. Other studies also support the hypothesis that cardiac epithelium may precede the occurrence of specialized intestinal metaplasia. It remains unclear whether cardiac-type epithelium in Barrett's esophagus arises from squamous epithelium or from migration of native cardiac epithelium at the EGJ into the distal esophagus. Experimental animal models of chronic reflux esophagitis, although with some shortcomings when researchers extrapolate the study data to the human situation, have provided interesting insights into possible mechanisms associated with the occurrence of Barrett's esophagus. A better understanding of the molecular mechanisms regulating the development of Barrett's esophagus is necessary for developing new strategies directed toward prevention and treatment of this metaplastic condition with a potential risk for malignant transformation.     

Etiology of intestinal metaplasia at the gastroesophageal junction

Background: Intestinal metaplasia occurs in the esophagus as a consequence of gastroesophageal reflux disease and in the stomach secondary to H. pylori infection. The etiology of intestinal metaplasia limited to the gastroesophageal junction or cardia (CIM) is disputed. We hypothesized that CIM has dual etiologies: gastroesophageal reflux in some, H. pylori infection in others, and that cytokeratin immunostaining can help to differentiate between these two etiologies. Methods: We defined CIM as the presence of intestinal metaplasia within cardiac mucosa on biopsy from an endoscopically normal-appearing gastroesophageal junction. Thirty patients with CIM who had multiple biopsy specimens taken from the esophagus, gastroesophageal junction, and stomach were identified. Tissue blocks from biopsy specimens taken at the gastroesophageal junction were sectioned and immunostained for cytokeratins 7 and 20. The cytokeratin 7/20 staining of the CIM in each patient was determined to be either a Barrett's or non-Barrett's pattern. H. pylori infection was assessed by Giemsa staining of antral biopsy specimens. Results: H. pylori infection was present in 16 patients. A Barrett's cytokeratin 7/20 staining pattern in the CIM was present in only 46% of the H. pylori–positive patients, as compared to 86% in the 14 patients with CIM and no H. pylori (p = 0.025). Objective evidence of reflux disease was present in 71% of patients with CIM and no H. pylori, as compared to 31% of patients with H. pylori. Conclusions: The two different patterns of cytokeratin 7/20 staining found in patients with CIM support the concept of dual etiologies for CIM. A Barrett's staining pattern was associated with objective evidence of gastroesophageal reflux and the absence of H. pylori, suggesting that cytokeratin 7/20 immunostaining is useful to determine the likely etiology of CIM.     

Hepatocyte antigen as a marker of intestinal metaplasia

Intestinal metaplasia is a histologic hallmark of Barrett's esophagus and chronic gastritis. Intestinal metaplasia may progress to dysplasia or carcinomas without proper treatment. Most cases of intestinal metaplasia are easily recognized on hematoxylin and eosin-stained sections. However, some cases of intestinal metaplasia may be hard to recognize if they lack the characteristic mucin-producing cells and Paneth cells, or if they are small in size. Recently, keratin 7, keratin 20, and MUC2 expression patterns were reported to be useful in confirming the diagnosis of intestinal metaplasia. We studied hepatocyte (Hep) antigen (a hepatocellular antigen mainly expressing in normal and neoplastic hepatic tissues) in 33 cases of Barrett's esophagus (9 cases associated with esophageal adenocarcinoma) and 13 cases of chronic gastritis associated with intestinal metaplasia and gastric adenocarcinoma. Hep monoclonal antibody recognizes intestinal metaplasia in all cases. We also compared expression of Hep with that of keratin 7, keratin 20, and MUC2 in intestinal metaplasia. The specificity and sensitivity of Hep for intestinal metaplasia were higher than that of keratin 7 and keratin 20, or MUC2. We conclude that Hep may be used as a single diagnostic marker for intestinal metaplasia.     

Gallbladder intestinal metaplasia in Pakistani patients with gallstones

The gallbladder specimens of patients who underwent cholecystectomy for symptomatic gallstones between 2003 and 2005 were evaluated for the presence of Intestinal Metaplasia. (IM) and its risk factors. IM was positive in 39% of 293 patients tested, and in the comparative analysis of 114 metaplasia positive versus 179 negative patients, a high risk was found in patients who were 60 years or older [adjusted odds ratio (aOR) = 3.0, 95% confidence interval (CI): 1.5, 6.2]. Other factors with aOR greater than 1 were moderate to excessive use of chilies (1.8) and ethnic origin of North India (1.7). Screening method has yet to be devised for early detection of gallbladder cancer by identifying metaplastic lesions early in life. We believe that large geographic variation and lifestyle environmental factors associated with the development of gallbladder metaplasia and cancer mortality are concealed in our study that needs to be further explored.     

Laparoscopic Nissen fundoplication and esophageal intestinal metaplasia: preliminary observations

The aim of this preliminary study conducted in a few cases was the retrospective evaluation of the effects of laparoscopic Nissen fundoplication on oesophageal intestinal metaplasia. Seventy-seven patients with hiatal hernia underwent digital videofluorography, endoscopy with biopsies, motility studies and 24-h oesophageal pH-monitoring. On the basis of the results of the diagnostic procedures and considering the patients' ages and response to proton-pump inhibitor treatment, 8 patients underwent laparoscopic Nissen fundoplication; in 5 cases intestinal metaplasia was present at histopathological examination. Two of these had Barrett's oesophagus at endoscopy and intestinal metaplasia was associated with low-grade dysplasia in both at histology; the other 3 did not present a columnar mucosa at endoscopy and 1 had low-grade dysplasia. In all 5 patients, at 1 year postoperative histopathological control, disappearance or decrease of metaplastic epithelium and regression of dysplasia were noted, with excellent results in terms of reflux symptoms at clinical control. On the basis of these preliminary data, it is our opinion that antireflux surgery is not only a suitable treatment in the management of Barrett's oesophagus but also has a favourable effect on intestinal metaplasia regression when a normal oesophageal mucosa is present.     

胃黏膜肠上皮化生的研究进展

胃黏膜肠上皮化生(IM)普遍认为是胃腺癌多阶段发生模式的中间阶段,已被视为癌前病变。IM有多种发病因素,且有越来越多的分子被证实参与了其发生机制。流行病学证据显示IM可能具有可逆性,但是目前仍存在争议。笔者就IM的病因、分子机制、是否可逆等方面等研究进展综述文献。     

Specialized intestinal metaplasia in patients with gastro-oesophageal reflux disease

BACKGROUND: There is an increasing awareness that short (less than 3 cm) segments of Barrett's epithelium and macroscopically normal cardia epithelium may harbour specialized intestinal metaplasia (SIM), a premalignant phenotype. The prevalence of SIM was studied prospectively in an unselected population of patients attending for endoscopy, and the association of SIM with symptoms, lifestyle, medication, endoscopic oesophagitis and carditis was investigated. METHODS: Two hundred consecutive patients underwent endoscopy. Biopsies taken from just below the squamocolumnar junction were stained for SIM, and were analysed for carditis and Helicobacter pylori infection. A detailed questionnaire of symptoms, tobacco consumption and the use of proton pump inhibitors was completed. RESULTS: Forty-two patients (21 per cent) had SIM: 19 (15 per cent) of 126 in an endoscopically normal oesophagus, 15 (24 per cent) of 63 in a short segment of Barrett's epithelium and eight of 11 in classical Barrett's oesophagus. There was a significant association between SIM and carditis (P < 0.0001) and endoscopic oesophagitis (P = 0.03). CONCLUSION: SIM is prevalent in patients undergoing endoscopy, does not correlate with symptoms or H. pylori infection, but is significantly associated with endoscopic and pathological markers of gastro-oesophageal reflux.