陕北胃癌高发区胃黏膜组织中MAD2的表达及意义

目的：研究MAD2在正常胃黏膜、胃病变黏膜组织中的表达,并探讨其与浅表性胃炎、萎缩性胃炎、不典型增生、胃癌之间的关系。方法：应用免疫组织化学sP法检测219例不同胃组织标本中MAD2的表达情况,所有标本均经病理证实。结果：MAD2在正常胃黏膜、浅表性胃炎、萎缩性胃炎、不典型增生、胃癌黏膜组织中的阳性表达率随病理学分类的不同而有差异。其中不典型增生、胃癌黏膜组织中MAD2的阳性表达率与其余各组MAD2的阳性表达率有明显的差异（P〈0．05）。结论：胃病变组织中MAD2蛋白的异常高表达,对诊断不典型增生、胃癌有重要的参考意义。     

环氧合酶-2在胃癌与癌前病变和其他胃黏膜组织中表达的研究

目的:研究胃癌与癌前病变和其他胃黏膜组织中环氧合酶-2(COX-2)的表达情况,探讨COX-2蛋白作为肿瘤分子标记物对胃癌和癌前病变进行辅助诊断的意义.方法:收集胃镜活检的正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎、胃黏膜肠化生、胃黏膜不典型性增生和胃癌组织,用免疫组织化学染色法检测COX-2蛋白在各种组织中的阳性表达情况.以正常胃黏膜组织和正常兔血清作阴性对照.结果:COX-2蛋白在胃癌前病变和和胃癌组织中的表达阳性率为48%-84%.胃癌和胃黏膜不典型性增生标本中COX-2蛋白表达阳性率显著高于正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎和胃黏膜肠上皮化生标本(P<0.05).而胃癌组织COX-2蛋白表达的阳性率与胃黏膜不典型性增生组之间无显著性差异(P>0.05).此外,慢性萎缩性胃炎和胃黏膜肠化生标本与正常胃黏膜和慢性浅表性胃炎标本之间COX-2蛋白表达阳性率亦有显著性差异(P<0.05);所有病变组的COX-2蛋白表达阳性率均比正常胃黏膜组显著性地升高 (P<0.05).结论:胃癌与癌前病变组织中COX-2蛋白的表达显著升高,COX-2蛋白可作为肿瘤标记物对胃癌和胃癌前病变进行辅助诊断.     

Cyclin D1和p16表达及Hp感染在胃癌发生中的作用和相关性研究

目的 探讨Hp感染及Cyclin D1和p16基因在胃癌发生过程中的作用及相关性.方法 用特殊染色法和免疫组化法检测正常及不同胃黏膜病变石蜡包埋标本.结果 (1)在正常黏膜、慢性浅表性胃炎、慢性萎缩性胃炎、不典型增生、胃癌中Hp感染率和Cyclin D1的表达率逐渐增高,p16表达率逐渐降低.其中正常胃黏膜组Hp感染率与慢性萎缩性胃炎组差异有显著性(P＜0.001),浅表性胃炎组Hp感染率与胃癌组差异有显著性(P＜0.005);慢性浅表性胃炎组Cyclin D1的表达率与不典型增生组差异有显著性(P＜0.005);正常黏膜组p16阳性表达率与胃癌组差异有显著性(P＜0.005).(2)在55例胃癌标本中Hp阳性组Cyclin D1阳性表达率高于Hp阴性组(P＜0.01),Hp阳性组p16阳性表达率低于Hp阴性组(P＜0.05),Cyclin D1阳性组p16阳性表达率低于Cyclin D1阴性组(P＜0.05).结论 胃癌的发生受Hp、Cyclin D1和p16等多因素及相互作用的影响.     

胃癌及癌前病变细胞凋亡与Caspase-9,Bax表达的关系

目的:探讨细胞凋亡基因Caspase-9和Bax在胃癌前病变和胃癌发展中的作用.方法:应用免疫组化S-P法检测 Caspase-9和Bax在57例胃癌及48例非癌胃黏膜组织的表达,用原位末端标记法(TUNEL法)检测相应胃组织细胞凋亡.结果:Caspase-9蛋白在非癌胃黏膜组(慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生)阳性表达率分别为 100.00%、86.67%、50.00%、42.85%,呈逐渐下降趋势.慢性浅表性胃炎组中Caspase-9蛋白阳性表达率与肠上皮化生、不典型性增生有显著性差异(P＜0.05),肠上皮化生组Caspase-9蛋白阳性表达率高于不典型增生组,但无统计学差异(P＞0.05).Bax蛋白在48例非癌胃组织中的阳性表达率分别为:慢性浅表性胃炎100.00%、慢性萎缩性胃炎80.00%、肠上皮化生56.25%、不典型增生57.14%,呈逐渐下降趋势,其中慢性浅表性胃炎组Bax蛋白阳性表达率与肠上皮化生、不典型增生有显著性差异(P＜0.05).慢性浅表性胃炎、慢性萎缩性胃炎 、肠上皮化生、不典型增生、胃癌组织中,AI值( 细胞凋亡指数)分别为(14.72±2.68)%、(10.02±2.34)%、(7.55±2.80)%、(6.09±2.35)%、(3.26±1.23)%,呈逐渐下降趋势,有显著性差异(P＜0.05).结论:Caspase-9和Bax可能参与胃癌癌前病变的形成,促进胃癌的发生.     

胃癌及癌前病变细胞凋亡与Caspase-9，Bax表达的关系

目的：探讨细胞凋亡基因Caspase-9和Bax在胃癌前病变和胃癌发展中的作用。方法：应用免疫组化S—P法检测Caspase-9和Bax在57例胃癌及48例非癌胃黏膜组织的表达,用原位末端标记法（TUNEL法）检测相应胃组织细胞凋亡。结果：Caspase-9蛋白在非癌胃黏膜组（慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生）阳性表达率分别为100．00％、86．67％、50．00％、42．85％,呈逐渐下降趋势。慢性浅表性胃炎组中Caspase-9蛋白阳性表达率与肠上皮化生、不典型性增生有显著性差异（P〈0．05）,肠上皮化生组Caspase-9蛋白阳性表达率高于不典型增生组,但无统计学差异（P〉0．05）。Bax蛋白在48例非癌胃组织中的阳性表达率分别为：慢性浅表性胃炎100．00％、慢性萎缩性胃炎80．00％、肠上皮化生56．25％、不典型增生57．14％,呈逐渐下降趋势,其中慢性浅表性胃炎组Bax蛋白阳性表达率与肠上皮化生、不典型增生有显著性差异（P〈0．05）。慢性浅表性胃炎、慢性萎缩性胃炎、肠匕皮化生、不典型增生、胃癌组织中,AI值（细胞凋亡指数）分别为（14．72±2．68）％、（10．02±2．34）％、（7．55±2．80）％、（6．09±2．35）％、（3．26±1．23）％,呈逐渐下降趋势,有显著性差异（P〈0．05）。结论：Caspase-9和Bax可能参与胃癌癌前病变的形成,促进胃癌的发生。     

血清与组织中MG7抗原表达对胃癌前病变风险预测的临床意义

背景与目的:多年来,许多科研人员致力于探索诊断胃癌及癌前疾病的生物学标志物.本研究通过对不同类型胃黏膜活检组织胃癌相关抗原(MG7-Ag)的表达和血清MG7-Ag含量的检测,探讨两者的相关性及对胃癌前病变风险预报的临床应用价值.方法:125例胃黏膜活检组织及其血清标本(正常胃黏膜12例,浅表性胃炎21例,胃黏膜糜烂溃疡24例,萎缩性胃炎15例,异型增生22例,胃癌31例),采用SP免疫组织化学二步法染色检测胃黏膜标本中MG7-Ag的表达情况;采用酶联免疫吸附实验检测血清MG7-Ag的含量.结果:①MG7-Ag在12例正常胃黏膜中无表达,在31例胃癌中表达率为93.55%,由浅表性胃炎(14.29%)或胃糜烂溃疡(33.33%)进展至萎缩性胃炎(86.67%)或异型增生(81.82%)再进展至胃癌(93.55%),MG7-Ag表达率依次逐渐上升,差异有显著性(P<0.05).②血清MG7-Ag含量从浅表性胃炎(3.0±0.6)、胃黏膜糜烂溃疡(2.8±2.0)、萎缩性胃炎(3.8±1.2)/异型增生(3.9±1.7)到胃癌组(7.0±4.6)有升高趋势,并且各组间比较差异均有非常显著性(P<0.01).胃癌患者血清MG7-Ag含量明显高于其他胃病患者,差异有显著性(P<0.05).③从浅表性胃炎到胃黏膜糜烂溃疡进展至萎缩性胃炎/异型增生再进展至胃癌,随着其病变组织MG7-Ag原位表达的上升,其血清MG7-Ag浓度有上升趋势,并且各组间比较差异均有非常显著性(P<0.01).两者具有良好的相关性(rs=0.346,P=0.001).结论:①MG7-Ag在胃疾病的动态表达提示胃黏膜细胞恶性程度与MG7-Ag的表达呈正相关,血清MG7-Ag与组织MG7-Ag表达有良好的相关性.②临床有望将MG7-Ag作为胃癌前病变随访,进行癌变风险预测以及早期诊断胃癌的预警标志物.③以血清标本代替组织标本检测UMG7-Ag具有取材方便,患者依从性好等优点,便于临床推广应用.     

胃癌组织AKT-2和PGC表达及其临床意义分析

目的:研究胃癌组织中丝氨酸/苏氨酸激酶(AKT-2)和胃蛋白酶原C(PGC)的表达及其临床意义分析。方法:应用免疫组化SP检测75例胃癌组织、20例萎缩性胃炎组织和15例正常胃黏膜组织标本中AKT-2蛋白和PGC的表达,采用χ2检验分析临床病理因素与上述指标的相关性。结果:胃癌、萎缩性胃炎和胃正常黏膜组织中AKT-2阳性表达率分别为70.7%(53/75)、38.9%(7/20)和26.7%(4/15),在胃癌组织中的表达明显高于萎缩性胃炎组织和胃正常黏膜组织(P值分别为0.003和0.001),但后两者之间差异无统计学意义(P=0.875),且与胃癌的分化程度、浸润深度、淋巴结转移及临床分期有关,P值分别为0.019,0.017,0.027和0.030;胃癌、萎缩性胃炎和胃正常黏膜组织中PGC阳性表达率分别为9.3%(7/75)、65.0%(13/20)和100.0%(15/15),在胃癌组织中的表达明显高于萎缩性胃炎组织和胃正常黏膜组织(P值分别为0.000和0.000),后两者差异有统计学意义(P=0.033),且与胃癌的分化程度及临床分期有关,P值分别为0.037和0.044;胃癌组织中AKT-2与PGC的表达存在负相关性,r=-0.297,P=0.01。结论:胃癌组织中AKT-2的表达明显高于萎缩性胃炎组织和胃正常黏膜组织,而胃癌组织中PGC的表达明显低于萎缩性胃炎组织和胃正常黏膜组织。因此,AKT-2的过表达及PGC的低表达在胃癌早期诊断中发挥重要作用。     

胃粘膜病变中HSP60的表达及其意义

目的通过研究HSP60在不同病变胃粘膜中的表达,以探讨HSP60与胃癌发生之间的关系及其在胃癌发生、发展过程中的作用.方法利用S-P免疫组织化学技术,对204例不同病变胃粘膜进行HSP60的检测.结果HSP60在胃癌组织的表达以强阳性和中等强度阳性为主,阳性表达率为73.5%,过表达率为57.1%;与浅表性胃炎和胃粘膜糜烂及溃疡相比差异显著(P＜0.01),与萎缩性胃炎及不典型增生相比差异不显著(P＞0.05),但两者过表达率之比差异显著(P＜0.05).结论不典型增生和胃癌组织中的HSP60表达显著高于浅表性胃炎和胃粘膜溃疡及糜烂组,胃癌组的HSP60过表达率显著高于萎缩性胃炎和不典型增生组,提示HSP60的过度表达发生在胃癌的进展过程中.     

幽门螺杆菌感染的胃黏膜上皮细皮细胞环氧合酶-2表达及意义

目的探讨幽门螺杆菌(Hp)感染的胃黏膜上皮细胞环氧合酶-2(COX-2)的表达及其在胃黏膜癌变过程中的意义.方法采用快速尿素酶试验和组织学碱性品红染色法检测胃黏膜Hp 感染状况;应用免疫组化法检测胃黏膜上皮细胞COX-2表达状况.结果 32例胃癌中,COX-2表达阳性22例(68.7%).12例Hp阴性的胃黏膜中,有1例(8.3%)COX-2低表达;10例Hp阳性正常胃黏膜中,仅1例(10.0%)COX-2低表达;9例Hp阳性的胃黏膜充血水肿糜烂者中,有5例(55.6%)COX-2表达阳性,与Hp阴性者和Hp阳性正常胃黏膜者比较,差异有统计学意义(P<0.05);10例Hp阳性的轻度萎缩性胃炎伴轻度肠化生者中,COX-2表达阳性5例(50.0%);10例Hp阳性的中重度萎缩性胃炎伴中重度肠化生者中,COX-2表达阳性8例(80.0%);8例Hp阳性的中重度不典型增生者中,COX-2表达阳性6例(75.0%).中重度萎缩性胃炎伴中重度肠化生和不典型增生者的COX-2表达高于轻度萎缩性胃炎伴轻度肠化生者(P<0.05).结论 Hp感染诱导慢性浅表性胃炎黏膜上皮细胞的COX-2表达与黏膜损伤形成有关;根据胃癌发生模式,COX-2表达上调与Hp感染胃黏膜癌变发生相关,且可能在癌前病变形成早期阶段起作用.     

Survivin、PTEN、p53、Ki-67在胃癌前病变中的表达及相关性

目的 探讨凋亡抑制基因Survivin和抑癌基因PTEN、p53以及增殖核抗原Ki-67在胃癌及癌前病变组织中的表达及其相关性.方法 应用免疫组织化学SP法检测Survivin、PTEN、p53及Ki-67蛋白在10例正常胃黏膜组织、33例浅表性胃炎、30例萎缩性胃炎(无肠化)、33例萎缩性胃炎(伴肠化)、31例异型增生(轻度13例,中～重度18例)、25例胃癌中的表达.结果 Survivin、PTEN、p53及Ki-67蛋白在正常胃黏膜组织的阳性表达率分别为0%、100%、0%、0%,在浅表性胃炎的阳性表达率分别为0%、100%、0%、18%,在萎缩性胃炎(无肠化)中阳性表达率分别为0%、93%、0%、33%,在萎缩性胃炎(伴肠化)中阳性表达率分别为0%、91%、0%、39%.在轻度异型增生胃黏膜中的表达率分别为7%、77%、7%、54%,在中度异型增生胃黏膜中的表达率分别为20%、70%、30%、60%,在重度异型增生胃黏膜中的表达率分别为50%、63%、63%、75%,在胃癌组织中表达率分别为56%、60%、68%、88%.Survivin、p53在异型增生中和胃癌组织中有阳性表达,且二者在重度异型增生与胃癌组织间均无显著差异(P＞0.05).PTEN在各胃黏膜组织中均有表达,且表达率逐渐降低,其中异型增生与萎缩性胃炎及浅表性胃炎比较均有显著差异(P＜0.05),异型增生与胃癌组织之间无显著差异(P＞0.05).Ki-67在正常胃黏膜中不表达,在异型增生与胃癌组织间有显著差异(P＜0.05).在异型增生和胃癌组织中Survivin和p53蛋白的表达呈正相关(P＜0.05);与PTEN蛋白的表达呈负相关(P＜0.05);与Ki-67(Ⅲ～Ⅳ)表达呈正相关(P＜0.05).结论 Survivin、PTEN、p53、Ki-67蛋白在胃癌的发生、发展中起协同作用.对其进行联合检测有助于胃癌的早期诊断.     

Patterns of gastric atrophy in intestinal type gastric carcinoma

BACKGROUND: Multifocal atrophic gastritis (MAG) is currently considered a precancerous lesion leading to intestinal type gastric carcinoma. The current study aimed to describe the topography of atrophy in stomachs with early gastric carcinoma. METHODS: Resected stomachs from patients with intestinal type gastric carcinoma were routinely processed, sectioned (an average of 108 sections/stomach), and stained with a triple stain. Sections were scored on a visual analog scale for Helicobacter pylori and intestinal metaplasia. The type of epithelium (antral, oxyntic, transitional) was recorded. Atrophy was defined as the loss of normal glandular components and included intestinal metaplasia and/or pseudo-pyloric metaplasia of the corpus. Pseudo-pyloric metaplasia was identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum. RESULTS: Sixteen stomachs with intestinal type gastric carcinoma were examined. In none of the specimens examined was MAG (independent foci of atrophy) identified. In the majority (88%), atrophy was present as a continuous sheet. Islands of intestinal metaplasia (multifocal intestinal metaplasia) were present within a sheet of pseudo-pyloric metaplasia. A few specimens (12%) had a non-atrophic corpus with almost total replacement of antral epithelium with intestinal metaplasia. Multifocal dysplasia distant from the original tumor was found both in areas with and without intestinal metaplasia. CONCLUSIONS: Contrary to popular belief, atrophy in intestinal type gastric carcinoma is not present as independent foci, but rather as a continuous sheet. Previous studies failed to identify pseudo-pylori metaplasia as a marker for atrophy.     

Prognostic effects of the gastric mucosal microbiota in gastric cancer

Gastric cancer (GC) is one of the most common malignant tumors with a high incidence and mortality. Microbiota play a significant role in human health and disease. We aimed to investigate the prognostic value of the gastric microbiota in different stomach microhabitats. We used our previously published 16S rRNA gene sequence data. We retrospectively enrolled a cohort of 132 patients with GC with complete prognostic information and selected 78 normal tissues, 49 peritumoral tissues, and 112 tumoral tissues for microbiota analysis. Patients with different prognoses showed different gastric microbiota compositions and diversity. The association network of the abundant gastric microbiota was more complicated in patients with poor prognoses. In the peritumoral microhabitat of patients with good prognoses, Helicobacter was significantly increased, whereas Halomonas and Shewanella were significantly decreased relative to that in the peritumoral microhabitat of patients with poor prognoses. PiCRUSt analysis revealed that the peritumoral microbiota had more different Kyoto Encyclopedia of Genes and Genomes pathways than did the tumoral and normal microbiota. This study evaluated the long-term prognostic value of the gastric mucosal microbiota in patients with GC. These findings suggested that the characteristic alterations of the gastric mucosal microbiota may be markers for clinical outcomes in these patients.     

Surgical management of gastric perforation in the setting of gastric cancer

Background

Gastric perforation is a rare presentation of gastric cancer and is thought to be a predictor of advanced disease and, thus, poor prognosis. Guidelines do not exist for the optimal management strategy. We aimed to identify, review, and summarize the literature pertaining to perforation in the setting of gastric cancer.

Methods

A qualitative, systematic review of the literature was performed from January 1, 1985, to January 1, 2010. Searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were performed using search terms related to gastric cancer surgery. Abstracts were examined by two independent reviewers and a standardized data collection tool was used to extract relevant data points. Summary tables were created.

Results

Nine articles were included. Perforation was reported to occur in fewer than 5% of gastric cancer patients. Preoperative diagnosis of a gastric cancer was rated and occurred in 14–57% of patients in the papers reviewed. Mortality rates for emergency gastrectomy ranged from 0 to 50% and for simple closure procedures the rates ranged from 8 to 100%. Patients able to receive an R0 gastrectomy demonstrated better long-term survival (median 75 months, 50% 5-year) compared with patients who had simple closure procedures.

Conclusions

Gastric cancer patients presenting with a gastric perforation demonstrate improved overall survival with an R0 resection; however, implementation of this management technique is complicated by infrequent preoperative gastric cancer diagnosis, and inability to perform an oncologic resection due to patient instability and intra-abdominal contamination.

     

Expression of glutathione S-transferases in normal gastric mucosa and in gastric tumors

Glutathione S-transferases from both normal gastric mucosa and its matched gastric tumors from 10 different patients were investigated. The transferases were purified and subsequently the isoenzyme composition was studied. Glutathione S-transferase (GST)-pi was present in all specimens in large amounts. Class alpha GSTs were present in 9 out of 10 normal specimens and in six tumors. In malignant tissue, expression of GST-pi was increased at the expense of class alpha GST. In six patients, the ratio GST-pi/GST-alpha was higher in tumorous versus normal tissue. On a Western blot, using a monoclonal antibody, GST-mu was shown to be present in both normal and malignant tissue from four patients, the other six patients completely missed the enzyme in their gastric tissue. When present, GST-mu amounts to only a few per cent of total GST protein. GST-pi was quantified by densitometric analysis of Western blots, treated with a monoclonal antibody against GST-pi. Both total GST enzyme activity as well as the absolute amounts of GST-pi protein were significantly higher in the tumors, as compared to its matched normal mucosa. The importance of this overexpression of GST-pi was previously unknown. However, the frequent occurrence of this phenomenon in many refractory tumors, and as shown now also in gastric cancers, suggests a role for GST-pi in the mechanism of anti-cancer drug resistance.     

Surgical management of gastric perforation in the setting of gastric cancer

Background

Gastric perforation is a rare presentation of gastric cancer and is thought to be a predictor of advanced disease and, thus, poor prognosis. Guidelines do not exist for the optimal management strategy. We aimed to identify, review, and summarize the literature pertaining to perforation in the setting of gastric cancer.

Methods

A qualitative, systematic review of the literature was performed from January 1, 1985, to January 1, 2010. Searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were performed using search terms related to gastric cancer surgery. Abstracts were examined by two independent reviewers and a standardized data collection tool was used to extract relevant data points. Summary tables were created.

Results

Nine articles were included. Perforation was reported to occur in fewer than 5% of gastric cancer patients. Preoperative diagnosis of a gastric cancer was rated and occurred in 14–57% of patients in the papers reviewed. Mortality rates for emergency gastrectomy ranged from 0 to 50% and for simple closure procedures the rates ranged from 8 to 100%. Patients able to receive an R0 gastrectomy demonstrated better long-term survival (median 75 months, 50% 5-year) compared with patients who had simple closure procedures.

Conclusions

Gastric cancer patients presenting with a gastric perforation demonstrate improved overall survival with an R0 resection; however, implementation of this management technique is complicated by infrequent preoperative gastric cancer diagnosis, and inability to perform an oncologic resection due to patient instability and intra-abdominal contamination.

     

Sonic hedgehog expression in gastric cancer and gastric adenoma

Hedgehog protein is essential to gastrointestinal tract development, and disruption of the hedgehog signaling pathway is associated with gastrointestinal tumorigenesis. Here, we analyzed the degree of hedgehog expression in gastric cancer and precancerous tissue. From August 2005 to May 2006, 52 gastric cancers and 16 gastric adenomas were obtained from surgically or endoscopically resected specimens. Immunohistochemical staining using sonic hedgehog (Shh) antibody was performed in cancerous and noncancerous tissue portions. Hedgehog expression was assessed based on the summed scores of the intensity and proportion of Shh staining. According to Lauren's classification, Shh expression was stronger in the intestinal type than in the diffuse type (p<0.001). Although Shh expression was not related to the location, size, metastatic status, or mucin phenotype of the gastric cancer, the expression was stronger in the tubular type of gastric cancer than in the mucinous and signet-ring cell types (p=0.001). Shh expression was stronger in gastric adenoma than in the diffuse-type gastric cancer (p<0.001), but revealed no difference with that of the intestinal-type gastric cancer (p=0.30). Shh expression was strongest in all types of intestinal metaplasia of noncancerous tissues. Shh expression is related to the intestinal type of gastric cancer. The stronger Shh expression in intestinal metaplasia and gastric adenoma indicates that hedgehog protein is involved at an early phase of gastric carcinogenesis.