PTEN encoding product： a marker for tumorigenesis and progression of gastric carcinoma

AIM: To detect the expression of PTEN encoding productin normal mucosa, intestinal metaplasia (IM), dysplasia andcarcinoma of the stomach, and to investigate its clinicalimplication in tumorigenesis and progression of gastriccarcinoma.METHODS: Formalin-fixed paraffin embedded specimens from184 cases of gastric carcinoma, their adjacent normal mucosa,IM and dysplasia were evaluated for PTEN protein expressionby SABC immunohistochemistry. PTEN expression wascompared with tumor stage, lymph node metastasis, Lauren'sand WHO's histological classification of gastric carcinoma.Expression of VEGF was also detected in 60 cases of gastriccarcinoma and its correlation with PTEN was concerned.RESULTS: The positive rates of PTEN protein were 100 %(102/102), 98.5 %(65/66), 66.7 % (4/6) and 47.8 %(88/184)in normal mucosa, IM, dysplasia and carcinoma of the stomach,respectively. The positive rates in dysplasia and carcinomawere lower than in normal mucosa and IM (P＜0.01).Advanced gastric cancers expressed less frequent PTEN thanearly gastric cancer (42.9 % v567.6 %, P＜0.01). The positiverate of PTEN protein was lower in gastric cancer with thanwithout lymph node metastasis (40.3 % v563.3 %, P＜0.01).PTEN was less expressed in diffuse-type than in intestinal-type gastric cancer (41.5 % v557.8 %,P＜0.05). Signet ringcell carcinoma showed the expression of PTEN at the lowestlevel (25.0 %, 7/28); less than well and moderatelydifferentiated ones (P＜0.01). Expression of PTEN was notcorrelated with expression of VEGF (P＞0.05).CONCLUSION: Loss or reduced expression of PTEN proteinoccures commonly in tumorigenesis and progression of gastriccarcinoma. It is suggested that PTEN can be an objective markerfor pathologically biological behaviors of gastric carcinoma.     

survivin蛋白在胃癌及癌前病变中的表达和意义

目的探讨survivin蛋白在胃癌及癌前病变中的表达程度和意义。方法收集南方医科大学南方医院消化科及佛山市三水区人民医院消化内镜室诊断并经病理确诊的病例。分为慢性浅表性胃炎组、慢性萎缩性胃炎组、慢性萎缩性胃炎伴轻度不典型增生组、慢性萎缩性胃炎伴中度不典型增生组、胃癌组共5组,每组40例,测定survivin蛋白在各组中的表达程度。结果 survivin表达在慢性浅表性胃炎组平均分值0.075±0.267,阳性率7.5%;在慢性萎缩性胃炎组平均分值0.600±0.744,阳性率45%;在慢性萎缩性胃炎伴轻度不典型增生组平均分值2.075±1.980,阳性率70%;慢性萎缩性胃炎伴中度不典型增生组平均分值4.225±2.402,阳性率95%;在胃癌组平均分值5.750±3.614,阳性率97.5%。survivin表达在胃高分化腺癌中,平均分值2.500±0.707;中分化腺癌平均分值8.750±3.495;低分化腺癌平均分值5.522±3.654;粘液腺癌平均分值3.200±0.837;印戒细胞癌平均分值6.000±0.000。结论 survivin在慢性浅表性胃炎-慢性萎缩性胃炎-不典型增生-胃癌的过程中阳性表达逐渐增高;但其在胃癌中的阳性表达与性别及肿瘤的大小和组织的分化程度无关。     

Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis

AIM: Cyclooxygenase (COX)-2 is over expressed in gastrointestinal neoplasm. Helicobacter pylori (H pylori) infection is causally linked to gastric cancer. However, the expression of COX-2 in various stages of H pylori-associated gastric carcinogenesis pathway has not been elucidated. Therefore, the aim of this study was to clarify the role of H pylori induced COX-2 expression during carcinogenesis in the stomach. METHODS: Gastric biopsies from 138 subjects (30 cases of chronic superficial gastritis (CSG), 28 cases of gastric glandular atrophy (GA), 45 cases of gastric mucosal intestinal metaplasia (IM), 12 cases of moderate gastric epithelial dysplasia and 23 cases of gastric cancer) were enrolled. H pylori infection was assessed by a rapid urease test and histological examination (modified Giemsa staining). The expression of COX-1 and COX-2 in human gastric mucosa was detected by immunohistochemical staining. RESULTS: H pylori infection rate was 64.3% in GA and 69.5% in gastric cancer, which was significantly higher than that (36.7%) in CSG (P<0.05). The positive expression rates of COX-2 were 10.0%, 35.7%, 37.8%, 41.7% and 69.5% in CSG, GA, IM, dysplasia and gastric cancer, respectively. From CSG to GA, IM, dysplasia and finally to gastric cancer, expression of COX-2 showed an ascending tendency, whereas COX-1 expression did not change significantly in the gastric mucosa. The level of COX-2 expression in IM and dysplasia was significantly higher in H pylori-positive than in H pylori-negative subjects (P<0.01). CONCLUSION: COX-2 expression induced by H pylori infection is a relatively early event during carcinogenesis in the stomach.     

胃癌中幽门螺杆菌感染与原癌基因c—met表达及预后研究

目的　研究幽门螺杆菌(Hp)感染的胃癌(GC)组织中c-met表达及(Hp)感染对胃癌预后的影响。方法　经病理证实,不同病变胃粘膜145例以免疫组化检测c-met基因表达,以W-S法及快速尿素酶试验检测(Hp)感染。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,c-met基因表达率分别为25.53%,51.28%,61.54%,66.67%和68.42%,CAG+IM、DYS、GC均显著高于CSG(P＜0.05)。肠型胃癌c-met阳性表达与(Hp)感染密切相关。CAG+IM,DYS和GC组c-met阳性表达(Hp)感染者明显高于阴性组。(Hp)阳性者5年生存期显著短于(Hp)阴性者。结论　(Hp)感染和c-met表达与胃粘膜增殖和恶化有关,前者也与胃癌预后有关。     

胃癌及癌前病变组织中CD44v6表达的意义

目的探讨CD44v6基因表达与胃癌发生及胃癌生物学行为的关系.方法应用抗CD44v6蛋白的单克隆抗体,采用免疫组化ABC方法对正常胃粘膜(n=10)、各级胃粘膜异型增生(轻度n=16,中度n=12,重度n=14)、早期胃癌(n=16)及进展期胃癌(n=52)进行研究,并与胃癌类型、大小、有无淋巴结转移等作了比较分析.结果正常胃粘膜CD44v6为阴性,随着胃粘膜病变的进展,CD44v6蛋白的表达率逐渐升高,至进展期胃癌,表达率达到顶峰.轻、中、重度异型增生表达率分别为12%,33%,43%;早期胃癌及进展期胃癌的表达率分别为44%和73%.各级异型增生表达率之间的差异无显著性,而进展期胃癌表达率显著高于早期胃癌(P＜0.05),淋巴结转移组的表达率显著高于淋巴结未转移组(82%vs56%,P＜0.05),肠型胃癌的表达率高于弥漫型胃癌(78%vs56%,P＜0.05),CD44v6蛋白的表达与胃癌肿块大小无相关性.结论胃粘膜重度异型增生在CD44v6基因表达上已具有明显的潜在恶性趋势,CD44v6基因表达阳性的胃癌具有更强的浸润及淋巴结转移的能力.     

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。     

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.     

Expression of TFF2 and Helicobacter pylori infection in carcinogenesis of gastric mucosa

AIM: To investigate the expression of TFF2 and Helicobacter pyloriinfection in carcinogenesis of gastric mucosa.METHODS: The expression of TFF2 was immunohistochemically analyzed in paraffin-embedded samples from 119 patients with endoscopic biopsy and subtotal gastrectomy specimens of gastric mucosal lesions, including 16 cases of chronic superficial gastritis (CSG), 20 chronic atrophic gastritis (CAG),35 intestinal metaplasia (IN), 23 gastric epithelial dysplasia (GED) and 25 gastric carcinoma (CA), and Helicobacter pylori infection was detected by Warthin-Starry staining.RESULTS: 1:TFF2 was located in the cytoplasm of gastrk mucous neck cell. The expression of TFF2 was 100 %,100 %, 0, 56.5 % and 0 in CSGs, CAGs, INs, GEDs and CAs, respectively. 2: The value of TFF2 positive cell density in CSG with Helicobacter pyloriinfection was higher than that without Helicobacter pyloriinfection. (52.89±7.27vs46.49±13.04, P＞0.05); But the value of TFF2 positive cell density in CAG and GED with Helicobacter pyloriinfection was significantly lower than that without Helicobacter pylori infection (18.17±4.09 vs 37.93±13.80, P＜0.01 and 14.44±9.32 vs 24.84±10.22, P＜0.05).CONCLUSION: Increase of TFF2 expression in CSG is perhaps associated with the protective mechanism after gastric mucosal injury. Decrease of TFF2 expression in CAG possibly attributes to the decrease in the number of gastric gland cell expressing TFF2. Re-expression of TFF2 in gastric epithelial dysplasia implies that TFF2 possibly contributes to the initiation of gastric carcinoma. The effect of Helicobacter pylori on the expression of TFF2 depends on the status of gastric mucosa.     

Syndecan-1 and E-cadherin expression in differentiated type of early gastric cancer

AIM: To elucidate the role and alterations of syndecan-1 and E-cadherin expression in different cellular phenotypes of differentiated-type gastric cancers (DGCs). METHODS: A total of 120 DGCs at an early stage, and their adjacent mucosa, were studied both by immunohis-tochemistry. Syndecan-1 and E-cadherin were assessed by immunohistochemical staining with anti-syndecan-1 and anti-E-cadherin antibodies, respectively. Based on immunohistochemistry, DGCs and their surrounding mucosa were divided into four types: gastric type (G-type), ordinary type (O-type), complete-intestinal type (CI-type), and null type (N-type). RESULTS: Syndecan-1 expression was significantly lower in G-type cancers (29.4%) than in O-type (79.6%) and CI-type cancers (90%) (P<0.05, respectively), but E-cadherin did not show this result. In addition, syndecan-1 expression was significantly reduced in DGCs comprised partly of poorly differentiated adenocarcinoma or signet-ring cell carcinoma, compared to DGCs demonstrating papillary and/or tubular adenocarcinoma (P<0.05). G-type intestinal metaplasia (IM) surrounding the tumors was observed in 23.8% of G-type, 4.9% of O-type, and 6.7% of CI-type cancers (P<0.05; G-type vs O-type). Reduction of syndecan-1 expression was significant in G-type IM (25%) compared to non-G-type IM (75%; P<0.05). CONCLUSION: Loss of syndecan-1 plays a role in the growth of G-type cancers of DGCs at an early stage, and the reduction of syndecan-1 expression in IM surrounding the tumors may influence the growth of G-type cancer.     

贲门肠上皮化生组织中DAS-1蛋白表达与贲门癌的相关性研究

目的 探讨贲门肠上皮化生(IM)组织中DSA-1表达与贲门癌(GCA)发生的相关性.方法 采用免疫组化法分析65例GCA患者癌组织和距癌组织2 cm贲门IM组织、15例门诊患者贲门(齿状线下2 cm内)IM组织及25例门诊患者贲门炎性组织检测DAS-1蛋白表达.结果 GCA患者贲门IM组织中Ⅲ型占55.4%(36/65),显著高于门诊患者的13.3%(2/15,P<0.01).DAS-1蛋白在GCA癌组织中的表达率为78.5%(51/65),显著高于贲门IM组织[38.8%(30/80),P<0.01].从Ⅰ～Ⅲ型贲门IM组织中,DAS-1蛋白的表达率呈逐渐递增趋势,其中Ⅲ型为71.1%,显著高于Ⅰ型(0%,P<0.01).结论 DAS-1过表达的Ⅲ型贲门IM与GCA的关系密切,可能是GCA癌前病变的重要因素.     

热休克蛋白70在人胃腺癌发展过程中表达的意义

目的 探讨人胃腺癌发展过程中热休克蛋白70（HSP70）的表达与病理分型、浸润深度和淋巴结转移的关系。方法 应用免疫组织化学S-P法检测52例人胃腺癌组织中HSP70的表达。结果 胃腺癌和黏液腺癌的HSP70阳性率分别为64.29%和60.00%；高分化和低分化腺癌的HSP70阳性率分别为67.86%和50.00%；胃腺癌HSP70的阳性率在不同病理分型、不同分化程度的肿瘤之间差别均无显著意义。侵犯深度达浆膜和肌层的胃腺癌HSP70阳性率分别为75.68%和33.33%（P〈0.05）。有淋巴结转移和无淋巴结转移组中HSP70阳性率分别为73.33%和45.45%（P〈0.05）。结论 人胃腺癌HSP70中阳性率与淋巴结转移、侵犯深度有关，与病理分型无关。提示胃腺癌晚期HSP70的表达高于早期胃腺癌，检测核指标可为早期诊断胃腺癌提供理论依据。     

Expression of ornithine decarboxylase in precancerous and cancerous gastric lesions

AIM: To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. METHODS: We studied the expression of ODC in gastric mucosa from patients with chronic superficial gastritis (CSG,n = 32),chronic atrophic gastritis CAG,n = 43; 15 with and 28 without intestinal metaplasia (IM),gastric dysplasia (DYS,n = 11) and gastric cancer (GC,n = 48) tissues using immunohistochemical staining. All 134 biopsy specimens of gastric mucosa were collected by gastroscopy. METHODS: The positive rate of ODC expression was 34.4%,42.9%,73.3%,81.8% and 91.7% in cases with CSG,CAG without IM,CAG with IM,DYS and GC,respectively (P < 0.01),The positive rate of ODC expression increased in the order of CSG < CAG (without IM) < CAG (with IM) < DYS and finally,GC. In addition,ODC positive immunostaining rate was lower in well-differentiated GC than in poorly-differentiated GC (P < 0.05). CONCLUSION: The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions.     

Reduction of syndecan-1 expression in differentiated type early gastric cancer and background mucosa with gastric cellular phenotype

Background Syndecan-1 is known to play a role as a cell adhesion molecule, similar to E-cadherin, and is associated with the maintenance of epithelial morphology. The purpose of this study was to elucidate the role and alterations of syndecan-1 expression in comparison with those of E-cadherin in different cellular phenotypes of differentiated-type gastric cancers (DGCs).Methods A total of 80 DGCs at an early stage, and their adjacent mucosa, were evaluated by both immunohistochemistry and in situ hybridization. Syndecan-1 and E-cadherin were assessed by immunohistochemical staining with an anti-syndecan-1 and an anti-E-cadherin antibody, respectively. Based on immunohistochemistry, DGCs and their surrounding mucosa were divided into four types: gastric type (G-type), ordinary type (O-type), complete-intestinal type (CI-type), and null type.Results The expression sites of syndecan-1 mRNA mostly coincided with those of syndecan-1 protein. Syndecan-1 expression was significantly lower in G-type cancers (30%) than in O- (81%) and CI-type cancers (92%) (P = 0.0001 and P = 0.004, respectively), but E-cadherin did not show this result. In addition, syndecan-1 expression was significantly reduced in DGCs comprised partly of poorly differentiated adenocarcinoma or signet-ring cell carcinoma, compared to DGCs demonstrating papillary and/or tubular adenocarcinoma (P = 0.02). G-type intestinal metaplasia (IM) surrounding the tumors was observed in 21% of G-type cancers, in 0% of O-, and in 10% of CI-type cancers (P = 0.01; G-type vs O-type). Reduction of syndecan-1 expression was significant in G-type IM (25%) compared to non-G-type IM (75%; P = 0.02).Conclusions Syndecan-1 plays a role in the growth of G-type cancers at an early stage compared with E-cadherin changes, and the reduction of syndecan-1 expression in IM surrounding the tumors may influence the growth of G-type cancer.     

Expression of estrogen receptor and estrogen receptor messenger RNA in gastric carcinoma tissues

AIM: To study estrogen receptor (ER) and estrogen receptor messenger RNA (ERmRNA) expression in gastric carcinoma tissues and to investigate their association with the pathologic types of gastric carcinoma.METHODS: The expression of ER and ERmRNA in gastric carcinoma tissues (15 males and 15 females, 42-70 years old) was detected by immunohistochemistry and in situ hybridization, respectively.RESULTS: The positive rate of ER (immunohistochemistry)was 33.3% in males and 46.7% in females. In Borrmann Ⅳ gastric carcinoma ER positive rate was greater than that in other pathologic types, and in poorly differentiated adenocarcinoma and signet ring cell carcinoma the positive rates were greater than those in other histological types of both males and females (P＜0.05). The ER was more highly expressed in diffused gastric carcinoma than in non-diffused gastric carcinoma (P＜0.05). The ER positive rate was also related to regional lymph nodes metastases (P＜0.05), and was significantly higher in females above 55 years old, and higher in males under 55 years old (P＜0.05). The ERmRNA (in situ hybridization) positive rate was 73.3% in males and 86.7% in females. The ERmRNA positive rates were almost the same in Borrmann Ⅰ, Ⅱ, Ⅲ and Ⅳ gastric carcinoma (P＞0.05). ERmRNA was expressed in all tubular adenocarcinoma, poorly differentiated adenocarcinoma and signet ring cell carcinoma (P＜0.05). The ERmRNA positive rate was related to both regional lymph nodes metastases and gastric carcinoma growth patterns, and was higher in both sexes above 55 years old but without statistical significance (P＞0.05). The positive rate of ERmRNA expression by in situ hybridization was higher than that of ER expression by immunohistochemistry (P＜0.05).CONCLUSION: ERmRNA expression is related to the pathological behaviors of gastric carcinoma, which might help to predict the prognosis and predict the effectiveness of endocrine therapy for gastric carcinoma.     

ICAM-1,VCAM-1在Hp阳性良性胃粘膜病变及胃癌中的表达

目的观察ICAM-1及VCAM-1在Hp阳性良性胃粘膜病变及胃癌组织中的表达并探讨其可能临床和病理意义.方法良性病变胃粘膜33例(慢性胃炎患者胃粘膜23例,胃癌癌旁良性病变胃粘膜10例),胃癌组织10例,经冰冻切片SP免疫组化染色后,结果进行半定量分析.结果 Hp阳性的良性病变胃粘膜中粘液细胞表达ICAM-1者为42.4%(14/33),表达VCAM-1者为27.3%(9/33);基质表达ICAM-1者为84.8%(28/33),表达VCAM-1者为81.8%(27/33).胃癌癌细胞中这两种细胞粘附分子阳性表达的例数及积分均高于它们在良性病变胃粘膜粘液细胞中的表达(P＜0.05或P＜0.01);胃癌组织中这两种粘附因子阳性表达的积分高于它们在良性病变胃粘膜基质中的表达(P＜0.05);癌旁良性病变胃粘膜粘液细胞中VCAM-1阳性表达积分高于其在慢性胃炎患者胃粘膜中的表达.结论胃癌时ICAM-1和VCAM-1表达增高,但可能不足以产生针对肿瘤细胞的宿主免疫监视,反而有利于提高这些细胞的运动能力.