Serum progastrin and its products, gastric acid secretion and serum pepsinogen I in gastric cancer

BACKGROUND: Numerous studies have shown an association between Helicobacter pylori (Hp) infection and gastric cancer (GC). STUDY: This study was designed to determine the role of cytotoxin-associated gene A (CagA)-positive Hp infection, serum amidated gastrins and their precursor, progastrin, gastric acidity and serum pepsinogen I (PG-I) levels in gastric cancerogenesis in 74 cancer patients and in 77 age- and gender-matched controls. Serum IgG antibodies to Hp and CagA and levels of IL-8 and PG-I were measured by ELISA, while progastrin and amidated gastrin by specific radioimmunoassay. RESULTS: The overall Hp and CagA seropositivity in GC patients were significantly higher (82 and 60%) than in matched controls (61 and 27%, respectively). Progastrin and amidated gastrin levels over their cutoff points (122 and 32 pM, respectively) were found in a significantly larger number of GC (59.4 and 44.5%) than in controls (9.0 and 16.8%, respectively). Histologically, all these GCs with increased serum progastrin and amidated gastrins were of intestinal type and showed CagA and Hp seropositivity. Serum IL-8 and gastric pH, above their cutoff points (pH >4.5), and serum PG-I level below its cutoff point (44.2 microg/l) were observed in a significantly higher number of GC patients as compared to controls. CONCLUSIONS: (1) GC patients have higher Hp and CagA seroprevalence than matched controls, confirming that CagA-positive Hp infection is associated with higher risk of GC; (2) serum levels of amidated gastrins and their precursor, progastrin, as well as IL-8 are significantly higher, while serum PG-I levels are reduced in intestinal type GC compared to controls, and (3) determination of high serum progastrin, amidated gastrins and IL-8 combined with low serum PG-I may be useful biomarkers of GC.     

肌少症维生素D缺乏在类风湿关节炎合并糖皮质激素诱发骨质疏松中的临床研究

目的:探讨肌少症和维生素D缺乏在RA患者合并糖皮质激素诱发骨质疏松(GIOP)患者中的临床意义。方法:选2017年1月至2018年12月我院311例RA患者和158名正常健康者,并详细记录RA患者临床、实验室指标及糖皮质激素(GC)使用情况。以生物电阻抗法测四肢骨骼肌质量,化学发光法测血清25羟维生素D水平,双能X线骨密度吸收仪测腰椎和髋部骨密度(BMD)。采用χ^2检验、非参数检验、多元Logistic回归进行统计分析。结果:①RA患者OP发生率33.4%(104/311)高于对照组12.7%(20/158)(χ^2=23.267,P<0.01);311例RA患者GC使用率为56.6%(176/311),其中GIOP发生率40.9%(72/176)。RA患者中肌少症发生率61.7%(192/311)高于对照组9.0%(14/156)(χ^2=117.310,P<0.01)。RA患者维生素D缺乏发生率为81.7%(254/311)高于对照组38.0%(60/158)(χ^2=90.415,P<0.01)。②在不考虑是否使用GC的情况下,无肌少症RA患者OP发生率17.6%(21/119)低于肌少症患者OP发生率43.2%(83/192)(χ^2=21.601,P<0.01)。在未服用GC的RA中,无肌少症患者OP发生率9.8%(6/61)低于肌少症患者OP发生率35.1%(26/74)(χ^2=11.834,P<0.01);在使用GC的RA中,无肌少症RA患者OP发生率25.9%(15/58)低于肌少症患者OP发生率48.3%(57/118)(χ^2=8.103,P<0.01)。③不考虑是否存在维生素D缺乏情况下,未服用GC患者OP发生率23.7%(32/135)低于服用GC患者GIOP发生率40.9%(72/176)(χ^2=10.161,P<0.01)。在维生素D不缺乏RA中,未服用GC患者OP发生率21.4%(6/28)与服用GC患者GIOP发生率31.0%(9/29)差异无统计学意义(χ^2=0.678,P>0.05);在维生素D缺乏的RA中,未服用GC患者OP发生率24.3%(24/107)低于服用GC患者GIOP发生率42.9%(63/147)(χ^2=9.3702,P<0.01)。④在服用GC的RA中,与不发生GIOP组比,发生GIOP组患者的年龄(t=5.313,P<0.01)和Sharp评分(Z=2.999,P<0.01)更高、病程(Z=2.141,P<0.05)和GC使用时间(Z=2.460,P<0.05)更长,而ESR(Z=2.262,P<0.05)、CRP(Z=2.551,P<0.05)和BMI(t=2.425,P<0.05)更低,X线分期构成比更差(χ^2=12.484,P<0.01)。⑤多元Logistic回归显示:女性[OR(95%CI)=14.240(3.878,52.288),P<0.01]、年龄[OR(95%CI)=1.079(1.042,1.118),P<0.01]、肌少症[OR(95%CI)=1.079(1.192,5.120),P<0.05]是RA患者发生GIOP的危险因素。结论:RA患者服用GC比例约60%,GIOP发生率高达40.9%,与肌少症和维生素D缺乏密切相关。     

Helicobacter pylori and CagA status,serum gastrin,interleukin-8 and gastric acid secretion in gastric cancer

BACKGROUND: Despite numerous epidemiological studies, the association between Helicobacter pylori infection and gastric cancer (GC) remains unexplained. This study was designed to determine the seropositivity of H. pylori and cytotoxin-associated gene A (CagA), serum gastrin and interleukin-8 (IL-8) levels as well as basal intragastric pH and maximal histamine-induced gastric acid outputs (MAO) in a large series of GC patients and controls. METHODS: 337 GC patients (118 men and 219 women; median age 59.4; range 21-87) and 337 controls randomized for sex and age entered the study. Serum IgG antibodies to H. pylori and CagA and serum levels of IL-8 were measured by enzyme-linked immunosorbent assay, while serum-amidated gastrin was determined by specific radioimmunoassay and correlated with gastric luminal pH. RESULTS: The numbers of GC patients and controls involved in the study in various age groups, ranging from 20 to > 70 years, were similar, but overall H. pylori IgG seropositivity in GC patients was significantly higher (90.8%) than in controls (79.2%). The overall CagA seropositivity in GC patients was about double (58.2%) that in controls (25.2%). Serum gastrin levels over the calculated cut-off value (38.88 pM/L) were found in several-fold larger number in GC patients (48%) than in controls (8.3%) and. similarly, serum IL-8 values over the cut-off point (1.77 pg/mL) occurred in almost all (99.7%) GC patients but in only a few controls (0.3%). Basal intragastric pH above the cut-off point (pH = 4.50) was observed in about 58.2% of GC patients compared to 15.1% in controls, and strong correlation between the serum gastrin and gastric pH was found in GC but weak in controls. The cut-off value for MAO was 12.3 mml/h; MAO below this cut-off value occurred in 89.9% of GC patients and in only 4.7% of controls. A summary odds ratio (SOR) in GC for H. pylori IgG was 2.59 (95% Cl: 1.61-4.22) for CagA - 4.12 (95% Cl; 2.93-5.8), for serum gastrin - 10.25 (95%; 6.47-16.47) and for MAO - 15.2 (95% Cl; 9.45-39.82). Multivariable analysis of serum gastrin, IgG and CagA, and luminal pH and MAO values revealed that only gastrin and CagA have significant influence on GC formation (OR > 1 in logistic regression). CONCLUSIONS: 1. CG patients show significantly higher H. pylori IgG and CagA seropositivity than dyspeptic age- and gender-matched controls, confirming that gastric infection with CagA expressing H. pylori greatly increases the risk of GC. 2. Serum gastrin levels in GC but not in controls are correlated with the rise in intragastric pH, indicating that excessive gastrin release in GC is affected by lower intragastric pH. 3. Serum gastrin level and CagA seropositivity are significantly increased in the majority of GC patients, and are the only variables in multivariable analysis to have a predominant influence on GC formation, which suggests that both these parameters may be implicated in H. pylori-related gastric carcinogenesis. 4. H. pylori-infected GC patients produce significantly more IL-8 than do non-GC controls, probably reflecting CagA-positive H. pylori-associated gastritis.     

HER2基因扩增和蛋白表达与胃癌临床病理特征和预后的关系

背景：曲妥珠单抗在人表皮生长因子受体2（HER2）阳性胃癌分子靶向治疗中的作用已得到确认,研究HER2评分与患者临床结局的关系可确定哪些患者可能从曲妥珠单抗治疗中获益。目的：探讨HER2基因扩增和蛋白表达与胃癌临床病理特征和预后的关系。方法：应用美国食品药品管理局（FDA）认证的检测试剂盒和Hofmann等报道的共识小组推荐胃癌HER2评分系统．采用荧光原位杂交（FISH）和免疫组化方法（IHC）检测177例胃癌组织的IqER2基因扩增和蛋白表达。比较不同临床病理特征胃癌亚组间HER2阳性率的差异．以Kaplan—Meier生存曲线分析HER2与预后的关系。结果：177例胃癌组织中31例（17．5％）HER2阳性．肠型胃癌阳性率显著高于弥漫型,混合型胃癌（28．1％对12．5％,P=0．0109）．分化较好的胃癌阳性率显著高于分化较差的胃癌（37．0％对10．7％,P〈0．0001）。HER2与性别、年龄、肿瘤部位和TNM分期无关。HER2阳性与阴性者总体生存率无明显差异,但在分化较好的胃癌中,HER2阳性者预后差于HER2阴性者（P=0．0084）。结论：肠型胃癌和分化较好的胃癌是曲妥珠单抗治疗的主要候选人群。HER2尚不能作为独立指标判断胃癌预后。     

胃癌中幽门螺杆菌感染与胃粘膜增殖及凋亡研究

目的研究幽门螺杆菌(Hp)感染的胃癌(GC)发展中增殖细胞核抗原(PCNA)表达及细胞凋亡的关系和对胃癌预后意义。方法145例经病理证实,不同胃黏膜病变采用免疫组化检测PCNA基因表达及Warthinstarry法检测Hp感染。采用原位末端标记法(TUNEL)检测细胞凋亡。结果在浅表性胃炎(CSG)、萎缩肠化生胃炎(CAG+IM)、异型增生(DYS)、早期GC和进展期GC中,PCNA基因表达率分别为24.53%,46.28%,60.54%,57.67%和71.42%,CAG+IM、DYS、GC均显著高于CSG(P<0.05)。凋亡指数(AI)分别为(4.55±2.33)%、(6.43±5.60)%、(6.45±5.12)%、(6.55±4.80)%、(8.84±5.63)%,进展期GC显著高于CSG(P<0.05)。胃黏膜凋亡指数与PCNA表达强度有密切相关(P<0.05)。PCNA阳性表达与胃癌组织类型、浆膜浸润和淋巴结转移密切相关,而且BorrmannIV明显高于早期胃癌和BorrmannI,II(P<0.05)。PCNA阳性表达与肠型胃癌Hp感染有关。CAG+IM,DYS和GC组PCNA阳性表达中Hp感染者明显高于阴性者。Hp阳性者5年生存期显著短于Hp阴性者。结论Hp感染和PCNA表达与胃黏膜增殖和恶化有关,且与凋亡有相关性。Hp感染与胃癌预后有关。     

幽门螺杆菌cagA基因株与胃癌p53,bcl—2表达的研究

目的　通过研究幽门螺杆菌（Ｈｐ）及细胞毒蛋白相关基因Ａ 株〔ｃａｇＡ（＋ ）株〕感染与胃癌组织ｐ５３、ｂｃｌ２ 表达的相互关系，以探讨Ｈｐ 的可能致癌机制。　方法　聚合酶链反应（ＰＣＲ）检测９２ 例胃癌和２４ 例浅表胃炎组织石蜡标本Ｈｐ 和ｃａｇＡ（＋ ）株感染。用免疫组化方法检测全部标本的ｐ５３、ｂｃｌ２ 表达。　结果　（１）Ｈｐ 感染在胃癌和浅表胃炎病例间差异无显著性（７９４％ 及６６７％ ，Ｐ＞ ００５），而ｃａｇＡ（＋ ）株感染前者高于后者（９３２％ 及５００％ ，Ｐ＜ ００１）；（２）ｐ５３、ｂｃｌ２ 的表达在Ｈｐ（＋ ）与Ｈｐ（－ ）组之间差异无显著性，而ｃａｇＡ（＋ ）株感染组均显著高于ｃａｇＡ（－ ）株组（Ｐ＜００１）。　结论　胃癌的发生可能与不同Ｈｐ 菌株感染有关。产生细胞毒素的Ｈｐ 菌株〔ｃａｇＡ（＋ ）株〕与胃癌关系更密切，它可能是导致ｐ５３ 基因突变和ｂｃｌ２基因过度表达的原因之一。     

胃癌及癌前病变胃粘膜的粘液组织化学研究

本文应用粘液组织化学方法对168例肠化生、96例异型增生和89例胃癌胃粘膜活检标本进行观察,发现87.6％的胃癌和40.6％的异型增生组织有异常粘液分泌;不全结肠型肠化生和硫酸粘液阳性肠化生在癌旁和异型增生的检出率显著地高于萎缩性胃炎组(P<0.05);伴不全结肠型肠化生和伴其它型肠化生的胃癌患者平均年龄分别为59.5岁和54.4岁、男女比为6∶1和2.25∶1.结果提示有异常粘液分泌的异型增生、伴不全结肠型化生的异型增生、不全结肠型化生的高龄男性、伴不全结肠型化生的胃良性疾病和硫酸粘液阳性肠化生宜被看作是胃癌的癌前病变,其中前三组的癌变趋向性更大.     

肌少症和骨质疏松对类风湿关节炎患者脊柱骨质疏松性骨折的协同影响

目的探讨肌少症和骨质疏松(OP)对RA患者脊柱骨质疏松性骨折(OPF)发生的协同影响.方法选择389例住院的RA患者和同期156例年龄、性别相匹配的健康人,采用双能X线吸收测量(DEXA)法测定腰椎和髋部的骨密度(BMD),采用生物电阻抗法测定四肢骨骼肌质量,摄脊柱X线正侧位片并以半定量法进行脊柱骨折的判定.统计学方法:2组间计量资料比较采用t检验,组间率的比较采用x2检验,2项分类资料的多元回归分析采用Logistic回紧(backward LR法)分析.结果RA患者各测定部位BMD均低于对照组(P<0.01),RA组骨质疏松发生率(128/389,32.9%)高于对照组[(20/156,12.8%),χ^2=22.706,P<0.01];RA患者脊柱OPF发生率为21.6%(84/389),高于对照组中[(3.8%,6/156),χ^2=25.439,P<0.01].RA患者中肌少症的发生率为54.8%,高于对照组[(9.6%,15/156),χ^2=93.241,P<0.01];RA组肌少症合并骨质疏松的发生率(28.5%)高于对照组[(5.8%),χ^2=118.110,P<0.01 ].不同骨量(骨量正常、骨量减少、骨质疏松)分组间RA患者脊柱OPF发生率的差异有统计学意义(χ^2=43.373,P<0.01),且呈现出随着骨量逐渐降低,脊柱OPF发生率逐渐升高的趋势(χ^2=43.003,P<0.01).伴肌少症的RA患者脊柱OPF发生率(27.2%,58/213)高于无肌少症的RA患者[(14.8%,26/176),χ^2=8.833,P=0.003].根据骨质疏松和肌少症分组的3组间(1=无肌少症和骨质疏松;2=单纯肌少症或骨质疏松;3=肌少症合并骨质疏松)RA患者脊柱OPF发生率的差异有统计学意义(χ^2=33.832,P<0.01),且从第1组到第3组脊柱OPF的发生率有逐渐增高的趋势(χ^2=37.164,P<0.01).与未服用糖皮质激素(GC)组相比,服用GC组的RA患者具有更高的肌少症发生率(χ^2=7.136,P=0.008)、OP发生率(CI=10.900,P=0.004)和脊柱OPF发生率(χ^2=20.673,P<0.01).Logistic回归分析显示:高龄[OR(95%CI)=1.069(1.038,1.101),P<0.01]、服用GC[OR(95%CI)=3.169(1.679,5.984),P<0.01]、肌少症和骨质疏松[OR(95%CI)=2.113(1.430,3.124),P<0.01]的同时存在为RA患者发生脊柱OPF的危险因素.结论RA患者肌少症、骨质疏松和脊柱OPF的发生率均明显增高,且肌少症和骨质疏松对RA患者脊柱OPF的发生具有协同作用.     

老年人胃癌癌前变化的随访研究

目的 研究老年人胃癌癌前变化的胃癌发病率,确定老年人发生胃癌的危险因素. 方法 完成随访的287例对象入选时平均年龄(79.44±11.69)岁,其中男204例,女83例.在1980年1月至2009年6月期间胃镜病理诊断为胃癌癌前变化,每隔1～3年随访胃镜及活检.对发生胃癌的危险因素进行logistic回归分析,计算OR值及其95％可信区间. 结果 入选对象胃镜病理诊断萎缩性胃炎177例,肠化生75例(其中Ⅰ型36例,Ⅱ型20例,Ⅲ型19例),低级别上皮内瘤变35例.随访共发现胃癌21例,胃癌发生率为7.32％,年平均发生率0.75％.其中继发于萎缩性胃炎4例,胃癌发生率为2.26％,年平均发生率0.23％；Ⅰ型肠化生1例,胃癌发生率为2.78％,年平均发生率0.29％；Ⅱ型肠化生1例,胃癌发生率为5.00％,年平均发生率0.51％;Ⅲ型肠化生6例,胃癌发生率为31.58％,年平均发生率3.25％；低级别上皮内瘤变9例,胃癌发生率为25.71％,年平均发生率2.65％.有吸烟史、低级别上皮内瘤变和Ⅲ型肠化生分别是胃癌发生的危险因素. 结论 老年人胃癌癌前变化的胃癌年平均发生率为0.75％,吸烟、低级别上皮内瘤变和Ⅲ型肠化生是老年人发生胃癌的危险因素.应加强对老年人胃癌癌前变化的胃镜监测.     

幽门螺杆菌感染在胃癌及癌前病变中的研究

目的　研究胃癌及癌前病变与Hp感染的关系 ,以探讨Hp可能的致癌机制。 方法　经内镜和病理明确诊断的胃癌及癌前病变者共 5 48例 ,包括慢性浅表性胃炎 (CSG) 16 3例、慢性萎缩性胃炎 (CAG) 2 0 7例、肠上皮化生 (IM) 71例 ,异型增生(DYS) 4 5例及胃癌 (GC) 6 2例。每例均活检胃窦大小弯、胃角及胃体大小弯共 5块 ,以WS法检测Hp。结果　癌前病变及胃癌Hp感染均较高 ,CAG(4 2 .5 % ) ,IM(76 .1% ) ,DYS(88.9% )和GC(72 .5 % ) ,与CSG(2 3.9% )有显著性差异 (P <0 .0 5或P <0 .0 1)。随着年龄增大 ,CAG、IM、DYS和GC逐步增多 ,而且≥ 5 6岁年龄组IM、DYS和GC显著多于≤ 40岁组 (P <0 .0 5 ) ,但CSG则相反。肠型胃癌和Hp感染密切相关 (P <0 .0 5 ) ,从胃窦小弯和大弯、胃角及胃体小弯和大弯顺序 ,Hp感染随着CSG、CAG、IM、DYS和GC病变而增高 ,Hp感染部位也在上移 ,尤其在胃体小弯及大弯 ,IM、DYS和GC的Hp感染显著高于CSC部位 (P <0 0 5 )。结论　Hp感染是导致从胃炎→胃萎缩→肠化→异型增生→癌变序列发展的危险因子 ,肠型胃癌和Hp感染密切相关 ,胃镜检查应该多部位取活检作病理及Hp检测 ,尤其是高位     

Influence of COX-2 Inhibition by Rofecoxib on Serum and Tumor Progastrin and Gastrin Levels and Expression of PPARγ and Apoptosis-Related Proteins in Gastric Cancer Patients

Cyclooxygenase-2 (COX-2) expression and certain growth hormones, such as gastrin, have been related to gastric carcinogenesis, but little is known about the factors that enhance this COX-2 expression and whether specific blockade of this enzyme has any influence on tumor growth and progression. Our objective was to determine the influence of a specific COX-2 inhibitor, rofecoxib (Vioxx), on serum and tumor levels of gastrin and its precursor, progastrin, as well as on tumor gene expression of COX-2, peroxisome proliferator-activated receptor gamma (PPAR), and apoptosis-related proteins (Bax and Bcl-2, caspase-3, and survivin). Twenty-four gastric cancer (GC) patients entered this study and were examined twice, once before and then following a 14-day treatment with Vioxx at a dose of 25 mg twice daily. For comparison, 48 age- and sex-matched healthy controls and 24 similarly matched Helicobacter pylori (Hp)-positive subjects were enrolled and treated with Vioxx as GC patients. Serum levels of anti-Hp and anti-CagA antibodies as well as IL-8 and TNF- were measured by enzyme-linked immunosorbent assay (ELISA), while serum and tumor contents of progastrin and amidated gastrin were determined by specific RIA. Tumor gene and protein expressions of COX-2, PPAR, Bax and Bcl-2, caspase-3, and survivin were determined by RT-PCR and western blot. The overall Hp and CagA seropositivity in 24 GC patients was significantly higher (82% and 47%) than in 48 controls (61% and 22%) but not in 24 Hp-infected subjects (100% and 38%). Serum IL-8 and TNF- values were significantly higher in GC patients than in controls without GC or Hp-infected controls. Median serum progastrin and gastrin levels were found to be significantly higher in GC than in controls without GC and in Hp-positive subjects. Treatment of GC patients with Vioxx resulted in a significant decrease in plasma and tumor contents of both progastrin and gastrin, and this was accompanied by the increment in tumor expression of COX-2, PPAR, Bax, and caspase-3 with a concomitant reduction in Bcl-2 and survivin expression. We conclude that: (1) GC patients show significantly higher Hp and CagA seropositivity than age- and sex-matched controls, but not Hp-positive subjects, indicating that infection with cytotoxic Hp is linked to GC. (2) Serum progastrin and gastrin levels are signficantly higher in GC patients than in matched controls, confirming that both gastrins may be implicated in gastric carcinogenesis. (3) GC patients exhibit significantly higher levels of IL-8 and TNF- than non-GC controls and Hp-positive subjects, probably reflecting more widespread gastritis in GC. (4) COX-2, PPAR, Bcl-2, and survivin were overexpressed in gastric tumor, but the inhibition of COX-2 activity by Vioxx resulted in a significant reduction in serum and tumor levels of progastrin and gastrin and serum IL-8 and TNF- levels, suggesting that gastrin and proinflammatory cytokines could mediate the up-regulation of COX-2 in gastric cancerogenesis. (5) Vioxx also enhanced expression of COX-2, PPAR, Bax, and caspase-3, while inhibiting the expression of Bcl-2 and survivin, suggesting that COX-2 blockade might be useful in chemoprevention against cancer possibly due to enhancement of the PPAR- and proapoptotic proteins-dependent apoptosis and the reduction in progastrin/gastrin-induced promotion of tumor growth.     

胃癌幽门螺杆菌感染中c-met基因表达与增殖的关系及其预后

目的 研究c-met基因蛋白及增殖细胞核抗原（PCNA）在幽门螺杆菌（Hp)感染的胃黏膜病变演进中的表达及关系，探讨Hp感染对胃癌预后的意义。方法 采用免疫组织化学法检测145例经病理证实不同胃黏膜病变的c-met和PCNA基因表达，Warthin-Starry法检测Hp感染。结果 在浅表性胃炎（CSG）、萎缩肠化性胃炎、异型增生（DYS）、早期胃癌和进展期胃癌中，c-met和PCNA2种基因在萎缩肠化性胃炎、DYS、胃癌均显著高于CSG（P＜0．05）。对胃黏膜增殖程度与c-met和PCNA阳性表达强度的密切关系分析，表明两者有显著关联（P＜0．01）。c-met和PCNA阳性表达与胃癌组织类型、浆膜浸润和淋巴结转移密切相关，而且Borrmann Ⅳ明显高于早期胃癌（P＜0．05）。c-met－LI和PCNA－LI在胃癌中等级相关表达有极显著的相关性（P＜0．001）。c-met阳性表达与肠型胃癌Hp感染有关。萎缩肠化性胃炎、DYS和胃癌组c-met阳性表达中Hp感染者明显高于阴性者。Hp阳性者5年生存期显著短于Hp阴性者。结论 c-met和PCNA基因表达与胃黏膜增殖和恶化有关，c-met基因可能成为评估胃癌恶化和预后的1项新的重要指标。Hp感染和c-met表达与胃黏膜增殖和恶化有关，Hp感染与胃癌预后有关。     

Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer

AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann’s HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann’s HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but l     

Phenotype analysis by MUC2, MUC5AC, MUC6, and CD10 expression in Epstein-Barr virus-associated gastric carcinoma

Background Gastric marker mucins (MUC5AC and MUC6) and intestinal marker molecules (MUC2 and CD10) have been used to determine the cell lineage of epithelial cell of gastric carcinoma (GC). Methods To clarify the characteristics of Epstein-Barr virus (EBV)-associated GC, 18 cases were immunohistochemically evaluated along with 56 cases of EBV-negative GC. Results MUC2 expression was lower in EBV-associated GC: immunostaining grades 0, 1, 2, 3, and 4 were observed in 10, 6, 1, 1, and 0 cases of EBV-associated GC, respectively, and in 18, 11, 15, 6, and 6 cases of EBV-negative GC, respectively (P = 0.013). CD10 positivity (grades 2–4) in EBV-associated GC was 6%, significantly lower than in EBV-negative GC (34%) (P = 0.030). When phenotypes of GC were categorized by the combined positivities of gastric markers (either MUC5AC or MUC6) and intestinal markers (either MUC2 or CD10), EBV-associated GC included primarily null (44%) and gastric (39%) types, but EBV-negative GC comprised null (7%), gastric (30%), intestinal (27%), and mixed (36%) types. The age of patients with gastric types was significantly younger for both EBV-associated GC and EBV-negative GC cases. Conclusions Neoplastic epithelial cells of EBV-associated GC did not express MUC2 or CD10, and most of them were categorized as null or gastric types. EBV infection may occur in the epithelial cells of null or gastric phenotypes, which may be devoid of transdifferentiation potential toward intestinal phenotypes.     

Epstein-Barr virus is associated with gastric carcinoma： The question is what is the significance？

AIM： To examine the possible role of the Epstein-Barr Virus （EBV） in the development of gastric adenocarcinoma （GC）. It is unclear whether EBV is involved in GC development or is a consequence of gastric inflammation secondary to immunosuppressive treatments. METHODS： A systematic review was carried out of all published observational studies on the temporal association between EBV and GC, with a view to determine a causal relationship. RESULTS： The present study showed that the worldwide crude prevalence of EBV in gastric adenocarcinoma was 8.29%. The prevalence varied from 7.08% for intestinal type and 9.82% for diffuse type of GC. It was observed that Western and Central Asian countries had a significantly higher frequency of EBV positive cases compared to South-Eastern countries. America had the highest EBV-GC prevalence whereas Europe had the lowest. CONCLUSION： The present review has demonstrated a high prevalence of EBV in gastric adenocarcinoma. However, studies designed to assess a temporal relationship and histological association using sensitive techniques should be carried out to establish the role of EBV in GC carcinogenesis.     

RhoC基因的过量表达在胃癌中的意义

目的探讨RhoC基因在胃癌中的表达及其与临床病理因素之间的关系。方法采用免疫组化S-P法检测97例胃癌组织及89例癌旁组织中RhoC的表达。结果在89例癌旁组织中82例不表达RhoC,97例胃癌组织中,75例(77.31%)表达RhoC。两者之间有显著差异(P=0.00)。RhoC蛋白的过量表达与患者性别及肿瘤分级、分化和淋巴结转移未见相关性,与肿瘤浸润深度,肿瘤分期存在相关性(P<0.05)。结论RhoC蛋白在胃癌中过量表达与胃癌的发生发展密切相关,可以作为胃癌的预后判断指标之一。     

Intestinal metaplasia and gastric carcinoma: A histological study of 198 gastrectomy specimens

One hundred and ninety-eight consecutive gastrectomy specimens (78 gastric carcinomas, 120 benign lesions) were reviewed and examined to study the relation between intestinal metaplasia (IM) and gastric carcinomas (GC). IM was classified as complete (type I) and incomplete (types II and III) depending on the types of mucin secreted. Only type III IM was found to be significantly associated with GC ( P = 0.0005) when GC was treated as a group in contrast to non-neoplastic lesions. On subdivsion into different types of GC, such association was only found in the intestinal type but not the diffuse type. The significance of the association between type III IM and the intestinal type GC is discussed. In addition, dysplasia was significantly associated with GC and not with benign lesions ( P < 0.005).     

Clinical significance and usefulness of soluble heparin binding-epidermal growth factor in gastric cancer

AIM:To evaluate the clinical usefulness of solubleheparin-binding epidermal growth factor(s HB-EGF)as a serum biomarker for gastric cancer(GC).METHODS:Serum s HB-EGF levels were measured by a commercially available human HB-EGF ELISA Kit and compared among 60 normal controls,30 highrisk patients,37 early gastric cancer(EGC),and30 advanced gastric cancer(AGC)through ANOVA test.Correlations between serum s HB-EGF and clinicopathological features of GC were analyzed through Spearman’s correlation.The diagnostic performance of serum s HB-EGF for GC was evaluated through receiver operating characteristic(ROC)curve and logistic regression analysis.RESULTS:Serum s HB-EGF levels were significantly higher in AGC group(314.4±127.5 pg/m L)than EGC(165.3±123.2 pg/m L),high-risk(98.7±67.3 pg/m L),and control(94.7±83.6 pg/m L)groups(post-hoc Bonferroni,all P0.001),respectively.Serum s HB-EGF levels were also significantly higher in EGC group than high-risk(P=0.049)and control(P=0.006)groups.Clinicopathologically,serum s HB-EGF levels closely correlated with depth of invasion(T-stage,γs=0.669,P0.001),lymph node metastasis(N-stage,γs=0.407,P=0.001),and distant metastasis(M-stage,γs=0.261,P=0.030).ROC curve and logistic regression analysis demonstrated a remarkable diagnostic potential of serum s HB-EGF.CONCLUSION:Serum s HB-EGF is closely correlated with advanced stage GC and can be a promising serological biomarker for GC.     

Expression of Span-21 and Ypan-21 in gastric cancer and subtypes of intestinal metaplasia

AIM: To analyze the relationship between intestinal metaplasia (IM) and gastric cancer (GC). METHODS: The expression of the Span-1 and Ypan-1 antigens in GC (n = 110) and IM (n = 343) specimens was examined using the ABC immunohistochemical technique. RESULTS: The expression rates of Span-1 and Ypan-1 in well and moderately differentiated adenocarcinoma (85.4% and 70.0%, respectively), signet-ring cell carcinoma (80.0%, 88.7%) and mucinous adenocarcinoma (88.6%, 76.5%) were significantly higher than the rates in poorly differentiated adenocarcinoma (48.6%, 45.9%), whereas the difference between early GC (59.2%, 65.4%) and advanced GC (73.8%, 65.5%) was insignificant. For IM, the expression of Span-1 was significantly higher in dysplasia, IM with GC, and chronic atrophic gastritis than in chronic superficial gastritis. In contrast, the expression of Ypan-1 was significantly higher only in IM with dysplasia (65.5%) than in chronic superficial gastritis (39.3%). When IM was classified into types I, II and III, the expression of both antigens in type III (79.0%, 75.2%) was higher than in type I (42.3%, 45.5%) and type II (51.2%, 50.0%), which themselves were similar. CONCLUSION: Span-1 and Ypan-1 may be of value in detecting GC, even in the early stage, and type III IM should be considered precancerous.