Expression of E—cadherin and β—catanin in gastric carcinoma and its correlation with the clinicopathological features and patient survival

AIM:The E-cadherin-catedin complex is important for cell-cell adhesion of epithelial cells.Impairment of one or more components of this comples is associated with poor differentiation and increased invasiveness of carcinomas,We evaluated the expression pattern of E-cadherin and β-catenin in gastric carcinoma and dysplasia and analyzed their relationship with tumor clinicopathological featrres and patient survival.     

CCR5 expression in inflammatory bowel disease and its correlation with inflammatory cells and β-arrestin2 expression

Objective: To elucidate the correlation of expression of CC chemokine receptor 5 (CCR5) with degrees of inflammatory cells infiltration and expression of β-arrestin2 in biopsic intestinal mucosa of the patients with inflammatory bowel disease (IBD).

Methods: Paraffin sections were derived from 53 patients with active IBD, 26 patients with remissive IBD and 30 healthy people. Immunohistochemical envision two-step method was used to test the expression of CCR5 and β-arrestin2 in biopsic intestinal mucosa. HE and toluidine blue staining were used to detect the pathological cytological analysis and classification in lamina propria of colonic mucosa.

Results: The positive rate, strong positive rate and immunohistochemical score of CCR5 expression in active IBD were significantly higher than that in normal controls and remissive IBD (p?<?.05). CCR5 expression had no obvious correlation with clinical severity, lesion distribution and endoscopic classification of active IBD. Neutrophils, eosinophils and lymphocytes in active IBD were significantly higher than that in normal controls and remissive IBD (p?<?.05), while the lymphocyte grade had a positive correlation with CCR5 expression (p?=?.042, r?=?.286). Mastocytes in active IBD, remissive IBD and normal controls had no obvious difference (p?>?.05). β-arrestin2 expression was significantly lower in active IBD than that in remissive IBD and normal controls, and it had a negative correlation with CCR5 expression (p?=?.01, r?=??.247).

Conclusions: CCR5 is highly expressed in active IBD, and it has positive correlation with lymphocyte grade and negative correlation with expression of β-arrestin2.     

Pin1 overexpression in colorectal cancer and its correlation with aberrant β-catenin expression

AIM: To investigate clinical significance of Pin1 and beta-catenin expression in colorectal cancers and to demonstrate the relationship of their expression. METHODS: The role of Pin1 and beta-catenin protein in colorectal tumorigenesis and their clinicopathologic significance were analyzed by immunohistochemistry, and the correlation between Pin1 and beta-catenin protein expressions was also studied in 124 patients with colorectal cancer who were surgically treated. RESULTS: Normal colonic epithelium either failed to express or showed focal and weak expression of Pin1 and beta-catenin. Overexpression of Pin1 and beta-catenin protein was found in 23 (18.54%) and 50 (40.3%) of 124 colorectal cancers, respectively. Overexpression of both proteins was not related to the lymph node metastasis, tumor stage and survival period after excision. Survival analysis results indicated that tumor stage was a valuable predictor of survival. Interestingly, a significant correlation was found between Pin1 and beta-catenin protein expression. CONCLUSION: Overexpression of Pin1 and beta-catenin may be closely related with the development and/or progression of colorectal carcinoma and further supports that Pin1 overexpression might contribute to the upregulation of beta-catenin.     

Pin1 overexpression in colorectal cancer and its correlation with aberrant β-catenin expression

AIM: To investigate clinical significance of Pin1 and β-catenin expression in colorectal cancers and to demonstrate the relationship of their expression. METHODS: The role of Pinl and β-catenin protein in colorectal tumorigenesis and their clinicopathologic significance were analyzed by immunohistochemistry, and the correlation between Pinl and β-catenin protein expressions was also studied in 124 patients with colorectal cancer who were surgically treated. RESULTS: Normal colonic epithelium either failed to express or showed focal and weak expression of Pinl and β-catenin. Overexpression of Pin1 and β-catenin protein was found in 23 (18.54%) and 50 (40.3%) of 124 colorectal cancers, respectively. Overexpression of both proteins was not related to the lymph node metastasis, tumor stage and survival period after excision. Survival analysis results indicated that tumor stage was a valuable predictor of survival. Interestingly, a significant correlation was found between Pin1 and β-catenin protein expression. CONCLUSION: Overexpression of Pin1 and β-catenin may be closely related with the development and/or progression of colorectal carcinoma and further supports that Pin1 overexpression might contribute to the upregulation of β-catenin.     

Expression of Survivin in pancreatic cancer and its correlation to expression of Bcl-2

AIM:To investigate the expression of Survivin in pancreaticcancer and its correlation to the expression of Bcl-2.METHODS:Survivin and Bcl-2 expressions were examinedby immunohistochemistry in 42 tissue samples frompancreatic cancer and 10 from normal pancrease.RESULTS:No survivin expression was detected in the tissuesamples from normal pancrease,while it was detected in34 of 42 tissue samples from pancreatic cancer (81.95%).There was a correlation between survivin expression anddifferentiation and stages of pancreatic cancer.Survivinpositive cases were strongly correlated to Bcl-2 expression(28/30 vs6/12,P<0.05).CONCLUSION:Overexpression of survivin plays animportant role in the development and progression ofpancreatic cancer,and correlates to the expression of Bcl-2.Survivin expression can be used as a prognostic factor.     

Effect of Helicobacterpyloriinfection on expression of BcI-2 family members in gastric adenocarcinoma

AIM:To investigate the effect of Helicobacter pylori (Hpylori)infection on the expressions of Bcl-2 family members ingastric adenocarcinoma.METHODS:Gastric adenocarcinoma and resection margintissues of 95 patients were studied.Semi-quantitative RT-PCRwas used to measure Bid,Bax and Bcl-2 mRNA expressions.RESULTS:Expressions of Bid and Bax in gastric adenocarcinomatissues without H pylori infection,with cagA~- H pylori infectionand cagA~ H pylori infection increased significantly in turn(Bid,0.304,0.422 and 0.855 respectively,P<0.05; Bax,0.309,0.650 and 0.979 respectively,P<0.05).Bcl-2 mRNAlevels increased significantly in gastric adenocarcinomatissues with cagA~- Hpylori infection and cagA~ Hpyloriinfection,compared with those without Hpylori infection(0.696 and 0.849 vs 0.411,P<0.05).Expressions of Bid,Bax and Bcl-2 in resection margin tissues without Hpyloriinfection,with cagA~- H pylori infection and cagA~ H pyloriinfection increased significantly in turn (Bid,0.377,0.686and 0.939 respectively,P<0.05; Bax,0.353,0.645 and1.001 respectively,P<0.05; Bcl-2,0.371,0.487 and 0.619respectively,P<0.05).In H pylori negative specimens,expressions of Bid and Bax correlated negatively with thatof Bcl-2 respectively in adenocarcinoma tissues (Bid vs Bcl-2,r=-0.409,P<0.05; Bax vs Bcl-2,r=-0.451,P<0.05).InH pylori positive specimens,expressions of Bid and Bax didnot correlate with that of Bcl-2 in adenocarcinoma tissues(Bid vsBcl-2,r=-0.187,P>0.05; Bax vs Bcl-2,r=0.201,P>0.05),but correlated positively with that of Bcl-2 respectivelyin resection margin tissues (Bid vs Bcl-2,r=0.331,P<0.05;Bax vs Bcl-2,r=-0.295,P<0.05).CONCLUSION:H pylori may enhance Bid,Bax and Bcl-2mRNA levels and cause deregulation of these apoptosis-associated genes expressions,which may play a role duringdevelopment of gastric adenocarcinoma induced by H pylori.     

Significance of effector protease receptor-1 expression and its relationship with proliferation and apoptotic index in patients with primary advanced gastric adenocarcinoma

AIM:To investigate the expression of effector proteasereceptor-1 (EPR-1),proliferative index ki-67 and apoptosisindex in patients with primary advanced gastricadenocarcinoma and to clarify the significance of EPR-1expression and its correlationship with the proliferationand apoptosis indexes.METHODS:Using immunohistochemical staining andterminal deoxynucleotidyl transferase mediated nick endlabelling (TUNEL) technique,we determined the expressionof EPR-1,proliferative index (Ki-67) and apoptotic index(AI) in 120 paraffin-embedded specimens of primaryadvanced gastric adenocarcinoma as well as lymph nodemetastasis and adjacent normal tissues.RESULTS:EPR-1 expression was distributed in thecytoplasm of normal gastric mycoderma,carcinoma cellsand smooth muscle cells.The positive rate of EPR-1expression in the primary gastric adenocarcinomas,invasiontumor node and lymph node metastasis was 65.83%,55.29%and 68%,respectively.While the positive rate in normalgastric mycoderma and smooth muscle cells was 46.7%and 53.3%,respectively.The average positive rate of ki-67in EPR-1-positive tumors was 7.00% which was significantlylower than that of 8.53% in EPR-1-negative tumors,butthe average AI in EPR-1-positive tumors was 1.25%,whichwas significantly higher than that of 1.00% observed inEPR-1-negative tumors.On the other hand,the averagepositive labeling index for Ki-67 (ki-67) in EPR-1-positivelymph node metastasis was 7.65%,which was significantlylower than that of 9.44% observed in EPR-1-negative lymphnode metastasis.However,the average AI in EPR-1-positivelymph node metastasis tumors was 0.99%,which wassignificantly higher than that of 0.67% observed in EPR-1-negative lymph node metastasis.CONCLUSION:The frequency of EPR-1 expression wassignificantly higher in primary gastric adenocarcinoma andin its lymph node metastasis than that in normal gastricmucosa.Expression of EPR-1 was significantly correlatedwith tumor histological subtypes and tumor differentiation.Weighted EPR-1 Score is positively correlated with apoptosis index,but is negatively related with proliferative index.Thus,Weighted EPR-1 Score and EPR-1 expression ingastric adenocarcinoma cells maybe a potential marker inclinical setting.     

Expression of Interleukin-11 and Interleukin-11 receptor a in human colorectal adenocarcinoma; Immunohistochemical analyses and correlation with clinicopathological factors

AIM: There is strong evidence that interleukin-11 (IL-11) is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11 receptor (IL-11R) has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma. METHODS: To elucidate the involvement of IL-11 and IL-11Ra in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immuno-histochemistry and Western blotting. RESULTS: Among 115 cases of adenocarcinoma, 100 cases (87.0%) showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases (75.6%) were positive for the IL-11Ra. Six cases (54.5%) and four cases (36.4%) of 11 adenomas were positive for IL-11 and IL-11Ra, respectively. The expression of IL-11Ra correlated with the histological differentiation (P=0.033503), the depth of tumor invasion (P=0.006395), Dukes' classification (P= 0.015648) and lymphatic invasion (P=0.003865). However, the expression of IL-11Ra was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Ra proteins. CONCLUSION: IL-11 and IL-11Ra are highly expressed in human colorectal adenocarcinoma and the IL-11Ra expression is correlated with clinicopathological factors. These findings suggest that the expression of IL-11Ra is an important factor for the invasion of human colorectal adenocarcinoma.     

Correlation of integrin β3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma

AIM： To investigate integrin β3 mRNA and vascular endothelial growth factor （VEGF） protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis. METHODS： In situ hybridization（ISH） of integrin β3 mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer. RESULTS： The positive rate of integrin β3 mRNA in non-tumor gastric mucosa （20%） was significantly lower than that of the gastric cancer tissue （52.5%, X^2 = 10.20, P 〈 0.01）. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of integrin β3 mRNA were significantly higher than those in patients of expanding type （P 〈 0.01）, stage T1-T2 （P 〈 0.01）, non-vessel invasion （P 〈 0.01）, without lymphatic metastasis （P 〈 0.01）, without hepatic and peritoneal metastasis （P 〈 0.01）, respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of VEGF protein were significantly higher than those in patients of expanding type （P 〈 0.01）, stage T1-T2 （P 〈 0.01）, non-vessel invasion （P 〈 0.01）, without lymphatic metastasis （P 〈 0.01）, without hepatic and peritoneal metastasis （P 〈 0.01）, respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type （P 〈 0.01）, stage T1-T2 （P 〈 0.01）, non-vessel invasion （P 〈 0.01）, without lymphatic metastasis （P 〈 0.01）, without hepatic and peritoneal metastasis （P 〈 0.01）, respectively. It was found that the positive expression rate of integrin β3 mRNA was positively related to that of VEGF protein （P 〈 0.01） and MVD （P 〈 0.05）,     

Expression of Interleukin-11 and Interleukin-11 receptor α in human colorectal adenocarcinoma; lmmunohistochemical analyses and correlation with clinicopathological factors

AIM: There is strong evidence that interleukin-11 (IL-11) is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11 receptor (IL-11R) has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma. METHODS: To elucidate the involvement of IL-11 and IL-11Ra in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting. RESULTS: Among 115 cases of adenocarcinoma, 100 cases (87.0%) showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases (75.6%) were positive for the IL-11Ra. Six cases (54.5%) and four cases (36.4%) of 11 adenomas were positive for IL-11 and IL-11Ra, respectively. The expression of IL-11Ra correlated with the histological differentiation (P = 0.033503), the depth of tumor invasion (P = 0.006395), Dukes'classification (P = 0.015648) and lymphatic invasion (P = 0.003865). However, the expression of IL-11Ra was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Ra proteins. CONCLUSION: IL-11 and IL-11Ra are highly expressed in human colorectal adenocarcinoma and the IL-11Ra expression is correlated with clinicopathological factors. These findings suggest that the expression of IL-11Ra is an important factor for the invasion of human colorectal adenocarcinoma.     

RhoGDI2、PAK2在胃癌中的原位表达及与临床病理特征的相关性

目的 检测RhoGDI2、PAK2在胃癌患者中的表达状况,评价其与胃癌临床病理特征的相关性,评估RhoGDI2、PAK2在胃癌侵袭、转移中的临床意义.方法 采用免疫组织化学技术(EliviSionTM二步法)检测103例胃癌标本中RhoGDI2、PAK2的表达.结果 胃癌组织中RhoGDI2和PAK2蛋白表达阳性率分别为72.82％、60.19％;RhoGDI2和PAK2在胃癌中的表达与胃癌分化程度、肿瘤浸润深度、淋巴结转移个数、有无远处转移和TNM分期密切相关,RhoGDI2和PAK2的表达呈正相关.结论 胃癌组织中RhoGDI2、PAK2的表达与胃癌侵袭、转移病理特征密切相关.RhoGDI2与PAK2可能共同参与调节胃癌的侵袭、转移过程.     

Overexpression of nuclear β-catenin in rectal adenocarcinoma is associated with radioresistance

AIM:To investigate the association between nuclearβ-catenin overexpression in rectal adenocarcinoma and radioresistance.METHODS:A retrospective analysis was conducted.The analysis involved 136 patients with locally advanced rectal adenocarcinoma who underwent shortcourse preoperative radiotherapy and radical resection.The expression ofβ-catenin in both pretreatment biopsy specimens and resected primary tumor tissues was examined by immunohistochemistry.The correlation ofβ-catenin expression with radioresistance was evaluated using the tumor regression grading(TRG)system.The relationship betweenβ-catenin expression and clinicopathological characteristics was also analyzed.Univariate and logistic multivariate regression analyses were adopted to determine the independent factors of radioresistance.RESULTS:Nuclearβ-catenin overexpression was more evident in radioresistant rectal adenocarcinoma than in radiosensitive rectal adenocarcinoma(57.6%vs 16.7%,P<0.001).Nuclearβ-catenin was overexpressed in favor of poor TRG(≤2),whereas membraneβ-catenin was expressed in favor of good TRG(≥3).Nuclearβ-catenin expression in tumor cell differentiation(P=0.018),lymph node metastasis(P=0.022),and TRG(P<0.001)showed significant differences.Univariate analyses demonstrated that radioresistance is associated with nuclearβ-catenin overexpression(P<0.001).In addition,logistic multivariate regression analysis indicated that only three factors,namely,tumor size(P<0.001),tumor cell differentiation(P<0.001),and nuclearβ-catenin overexpression(P<0.001),are associated with radioresistance.By using radioresistance as a prediction target,nuclearβ-catenin-based prediction alone achieved 83%accuracy,65%sensitivity,and88%specificity.CONCLUSION:Nuclearβ-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.     

Abnormal β-catenin immunohistochemical expression as a prognostic factor in gastric cancer: A meta-analysis

AIM: To evaluate the effect of β-catenin immunohistochemical expression on the prognosis of gastric cancer (GC).METHODS: We searched Pubmed and Embase to identify eligible studies. The search ended on November 10, 2013, with no lower date limit. The citation lists associated with the studies were used to identify additional eligible studies. We included studies reporting sufficient information to estimate the HR and 95%CI, and information to estimate the OR in the analysis of clinicopathological features. The qualities of these studies were assessed using the Newcastle-Ottawa Quality Assessment Scale. HRs and ORs and their variance were calculated and pooled using Review Manager Version 5.2.RESULTS: A total of 24 studies were identified and comprised 3404 cases. β-catenin expression was significantly correlated with poor overall survival (OS) in GC patients (HR = 1.85, 95%CI: 1.39-2.46), but showed a significant degree of heterogeneity (I² = 71%, P < 0.0001). Subgroup analysis indicated that an abnormal pattern of β-catenin expression had an unfavorable effect on OS (HR = 1.79, 95%CI: 1.39-2.32). However, accumulation in the nucleus or loss of membrane did not influence the survival of GC patients independently. Moreover, the combined OR of β-catenin indicated that β-catenin expression was associated with Lauren classification (OR = 1.98, 95%CI: 1.19-3.29), lymph node metastasis (OR = 2.00, 95%CI: 1.44-2.77), distant metastasis (OR = 2.69, 95%CI: 1.35-5.38) and grade of differentiation (OR = 2.68, 95%CI: 1.66-4.34). β-catenin expression did not correlate with TNM stage (OR = 1.34 95%CI: 0.96-1.86), the depth of invasion (OR = 1.48, 95%CI: 0.94-2.33) or vascular invasion (OR = 1.11, 95%CI: 0.70-1.76).CONCLUSION: Abnormal β-catenin immunohistochemical expression may be associated with tumor progression and could be a predictive factor of poor prognosis in patients with GC.     

Nonselective β-blockers may induce development of portal vein thrombosis in cirrhosis

Currently, nonselective β-blockers (NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in cardiac output by blockade of β1 receptors and vasoconstriction of the splanchnic circulation by the blockade of β2 receptors. The prognostic value of occlusive portal vein thrombosis (PVT) in cirrhotic patients has been increasingly recognized. The most important risk factor for the development of PVT in liver cirrhosis is the decreased portal vein inflow velocity. Collectively, we propose that the use of NSBBs potentially increases the development of portal vein thrombosis by reducing portal vein inflow velocity. The hypothesis should be confirmed by prospective cohort studies, in which cirrhotic patients without prior PVT treated with and without NSBBs are enrolled, and the development of PVT during follow-up is compared between the two groups. Additionally, subgroup analyses should be performed according to the dosage of NSBBs and the reduction of portal inflow velocity after use of NSBBs.     

c-ski在胃癌组织中的表达与临床因素相关性分析

目的探讨c-ski在胃癌组织中的表达与临床因素相关性分析。方法采用RT-PCR法和免疫组化法检测癌旁组织和胃癌组织中c-ski蛋白及mRNA表达情况。结果胃癌组织c-ski蛋白阳性率和c-skimRNA水平明显高于癌旁组织(P0.01);c-ski蛋白阳性率肠型胃癌明显高于弥漫型胃癌,差异具有统计学意义(P0.05)。c-ski蛋白阳性率与患者的性别、肿瘤的大小、浸润深度、是否有淋巴结及远处转移、1年的生存时间无关。结论 c-ski在胃癌组织中表达明显升高,且在弥漫型胃癌和肠型胃癌表达中存在差异。     

Hypermethylation of TGF-β1 gene promoter in gastric cancer

AIM:To examine transforming growth factor-β1(TGF-β1)promoter methylation in gastric cancer and to determine if Helicobacter pylori(H.pylori)or interleukin(IL)-1β could induce TGF-β1 hypermethylation in vitro.METHODS:We examined the frequency and extent of TGF-β1 promoter methylation using methylationspecific PCR in the gastric tissues from 47 gastric cancer patients and 39 non-gastric cancer subjects.H.pylori infection was confirmed by a positive result from either a serological test,histological analysis or C13urea breath test.GES-1 and MKN-45 cells co-cultured with H.pylori or treated with IL-1β for 12,24 and 48 h in vitro tested the effects of H.pylori or IL-1β on TGF-1β.RESULTS:Twenty-four/forty-seven(51%)cases of gastric cancer(GC)tissues showed TGF-β1 promoter methylation,15/47(31.9%)cases of matched noncancerous gastric mucosa tissues from the GC patients,and 11/39(28%)case of the normal gastric mucosa tissues from non-GC subjects showed TGF-β1 promoter methylation(51%vs 28%,P<0.05).Significantly higher levels of methylation of TGF-β1 were found in the tumor tissues than in non-tumor tissues from GC patients(0.24±0.06 vs 0.17±0.04,P<0.05)and normal gastric tissues from non-GC subjects(0.24±0.06 vs 0.15±0.03,P<0.05).TGF-β1 methylation was found in 48.3% of H.pylori-positive gastric mucosal tissues whereas only 23.1% of H.pylori-negative gastric mucosal tissues showed TGF-β1 methylation(48.3%vs 23.1%,P<0.05).IL-1β appeared to induce a dose-dependent methylation of TGF-β1 and the strongest methylation was observed in GES-1 cells treated with 2.5 ng/mL of IL-1β for 48 h.Further studies showed that pre-treatment of GES-1 cells with 20ng/mL IL-1RA for 1 h could partially abolish the effect of IL-1β on TGF-β1 methylation.Infection of GES-1cells by H.pylori was not found to induce significant TGF-β1 promoter methylation.CONCLUSION:Our data revealed that TGF-1 promoter is methylated in GC patients.IL-1β may be an important mediator for H.pylori induced gene methylation during GC