Expression of phosphorylated ERK1/2 and homeodomain protein CDX2 in cholangiocarcinoma

Purpose The extracellular signal-regulated kinase (ERK) 1/2 pathway plays important roles in the regulation of cell proliferation, differentiation and cell survival. The caudal-related homeobox protein CDX2 is essential for the development of the intestine, and is related to gastric and gallbladder cancers with the intestinal phenotype. However, the roles of ERK1/2 phosphorylation (pERK1/2) and CDX2 in cholangiocarcinogenesis remain unknown.Methods We investigated the expression of pERK1/2, CDX2 and MUC2 in Thai cholangiocarcinoma (CCA) specimens by means of immunohistochemical staining, and compared the expression of these proteins with clinicopathological factors.Results The pERK1/2 protein was expressed in 29 of 59 (49.2%) CCA cases. Interestingly, in tubular-type CCA, the frequency of pERK1/2 expression was associated with a higher grade of differentiation (P = 0.001). CDX2 expression was observed in 22 of the 59 (37.3%) CCA cases, showed a relationship with MUC2 expression (P = 0.001), and was much higher in papillary-type than tubular-type CCA (P = 0.002).Conclusion These results imply that pERK1/2 may be important for the differentiation of tubular-type CCA, while CDX2 is related to the intestinal phenotype of papillary-type CCA.     

Barrett食管黏膜微细形态改变和CDX2蛋白的表达

目的 研究食管黏膜微细形态的改变和CDX2蛋白表达在Barrett食管（BE）诊断中的意义。方法 采用高清晰内镜观察BE及非BE的胃食管反流疾病（GERD）患者的齿状线附近黏膜的小凹及微细血管形态变化，并采用免疫组化方法检测CDX2蛋白的表达。结果 48例BE中，40例可观察到食管下段的栅状血管末端有不同程度的下移现象，而60例非BE的GERD患者均未发现有血管下移现象；放大内镜下BE黏膜可分为绒毛型、条纹型和小点型，绒毛型肠上皮化生（肠化）检出率显著高于条纹型及点状（P〈0.01）；CDX2蛋白不但在肠化的杯状细胞表达，而且在BE和非BE的柱状上皮中亦有表达，绒毛状上皮CDX2表达的阳性率显著高于条纹状（P〈0.01）和点状上皮（P〈0．05）。结论 观察食管黏膜微细形态有助于对BE的诊断、分型及了解其相关病理背景，CDX2蛋白是一种具有较高敏感性的肠上皮特异标志物，有助于判断早期肠化的发生，对BE的早期诊断可能有重要价值。     

Expression of MUC2 in gastric carcinomas and background mucosae

BACKGROUND AND AIM: Gastric carcinomas contain elements of both intestinal and diffuse types. Such heterogeneous components may distort the evaluation of the role of the mucin MUC2 in gastric carcinoma. The role of MUC2 expression in background mucosa is not yet clarified. METHODS: We analyzed the expression of MUC2 in gastric mucosa and intestinal metaplasia adjacent to the tumoral area and carcinomas (n = 98) using immunohistochemistry. The immunoreactivity was quantified using an immunohistochemical scoring system. RESULTS: In the intestinal metaplasia adjacent to the tumoral area, MUC2 was detected in 76 (97.4%) of 78 intestinal metaplasia, and MUC2 expression was inversely associated with the depth of wall penetration (P = 0.026) and tumor stage (P = 0.021). Although the expression rate of MUC2 antigens was higher in intestinal-type adenocarcinoma than in diffuse-type adenocarcinoma, a significant correlation with pathologic staging of the TNM system (pTNM staging) and MUC2 expression could not be found in each subtype of gastric carcinomas. CONCLUSION: The expression of MUC2 in intestinal metaplasia was higher in tumors of earlier stages. These findings suggest that increased MUC2 expression in intestinal metaplasia in the neighborhood of the carcinomas may play an important role in gastric carcinomas. Further investigations regarding the role of MUC2 expression in gastric carcinoma and background mucosae are necessary.     

The Role of CDX2 in Intestinal Metaplasia Evaluated Using Immunohistochemistry

Background/Aims

Intestinal metaplasia (IM) has been regarded as a premalignant condition. This study evaluated the role of the transforming factor CDX2 according to the severity and type of IM.

Methods

This analysis was performed on 383 subjects with IM in the antrum and/or body, with diagnoses that were categorized as controls, dysplasias, and gastric cancers. The IM grades were classified into four groups as negative, mild, moderate or severe using the updated Sydney scoring system. The IM subtypes were categorized as type I, type II, and type III using high iron diamine and alcian blue (pH 2.5) staining. The CDX2 expression in the IM foci was evaluated using immunohistochemistry in specimens from the antrum and/or body.

Results

CDX2 expression increased according to IM severity (p=0.001) but was not associated with the IM subtype (p=0.881) in the antrum specimens. Similarly, CDX2 expression increased according to the IM grade (p=0.001) but was not associated with the IM subtype (p=0.755) in the body specimens. CDX2 expression was also increased according to baseline disease in the antrum, especially dysplastic and GC group (p=0.003), but not in the body (p=0.582). However, status of Helicobacter pylori infection was not associated with CDX2 expression in the antrum (p=0.692) and body (p=0.271).

Conclusions

These results show that CDX2 expression is associated with the IM grade regardless of the IM subtype and that it was more frequent in the dysplasia group. These results suggest that CDX2 expression might play an important role in the progression of IM in various environments that can affect neoplastic change.     

门诊护理干预对提高老年糖尿病病人生活质量评价分析

[目的]调查研究门诊护理干预对老年糖尿病病人生活质量的影响。[方法]采用随机法将50例老年糖尿病病人分为观察组和对照组各25例,两组病人采用相同的治疗方案,观察组采用门诊护理方法,对照组采用常规的护理方案进行护理。[结果]观察组在实施护理后的情绪明显好转,对疾病护理后的焦虑程度为35.56分±9.05分,与对照组的52.25分±7.12分比较,差异具有统计学意义(P<0.05)。两组病人的心率与血压状况相比存在较大的差异性(P<0.05)。[结论]通过门诊护理干预,可以有效提高老年糖尿病病人的生活质量,提高战胜疾病的信心。     

CDX2 MUC2在胃黏膜肠上皮化生组织中的表达情况及其临床意义研究

目的 探讨尾型同源盒转录因子2(CDX2)、黏蛋白2(MUC2)在胃黏膜肠上皮化生组织中的表达情况及其临床意义.方法 选择2011年1月至2014年5月于宁夏医科大学总医院消化内科就诊并行内镜活检的152例患者,根据病理检查结果将其分为非萎缩性胃炎组(32例)、萎缩性胃炎组(31例)、低级别上皮内瘤变组(24例)、高级...     

Relevance of high virulence Helicobacter pylori strains and futility of CDX2 expression for predicting intestinal metaplasia after eradication of infection

Abstract

Objective. Different Helicobacter pylori genotypes are associated with distinct inflammatory responses and consequent development of pre-neoplastic lesions, namely intestinal metaplasia (IM), which is dependent on the expression of CDX2. We aimed to evaluate IM progression/regression in the context of H. pylori eradication, bringing into play the effect of the virulence of infecting H. pylori strains and the hypothesis that CDX2 expression might be a marker for later development of IM. Material and methods. Sixty-five male volunteers were evaluated by endoscopy before H. pylori eradication and after a median six-year follow-up. Histological diagnosis was performed at baseline and follow-up, and baseline H. pylori genotypes and CDX2 expression in non-metaplastic foci were also assessed. Results. Fifty-one individuals remained free from infection at follow-up. Six out of 27 who had no metaplastic lesions at baseline developed IM. CDX2 nuclear expression was observed in 15 of the 21 cases (71.4%) showing no progression to IM, and in three out of six cases (50%) with progression to IM (p = 0.367). Six of the 24 cases with IM at baseline showed regression to less severe outcomes, which was less frequent in those infected with high-virulence strains (7.7% vs. 50%, p = 0.047). In the latter there is a significant persistence of lymphoid follicles. Conclusions. Our results support that under infection with high virulence H. pylori strains, IM is a point of difficult return in the gastric carcinogenic pathway. The appearance of CDX-expressing cells in non-metaplastic foci was not associated with the development of IM during the six-year follow-up.     

同源异形盒基因CDX2的表达与胃黏膜肠上皮化生类型的关系

目的:探讨CDX2表达与胃黏膜肠化生类型的关系.方法:利用免疫组化技术检测58例正常胃黏膜、184例肠化生和36例胃癌组织CDX2表达;利用HID-ABpH2.5-PAS将184例肠化生分为Ⅰ型81例, Ⅱ型62例和Ⅲ型41例.结果:正常胃黏膜CDX2阴性表达, 胃癌组织CDX2表达高于正常胃黏膜( P<0.01), 低于肠化生黏膜(59.8% vs 27.8%, P<0.01); Ⅰ型、Ⅱ型肠化生CDX2表达高于胃癌和Ⅲ型肠化生,差异均有统计学意义. 唾液酸黏蛋白着色的Ⅰ型肠化生CDX2呈清晰着色, 硫酸黏蛋白着色的Ⅲ型肠化生CDX2未见着色.结论:CDX2可作为判断肠化生分化程度的指标.     

Expression of cyclooxygenase-2 protein in colorectal carcinomas

Summary Background. Overexpression of cyclooxygenase-2 (COX-2) has been demonstrated in various human cancers, including colorectal cancer. Thus, overexpression of COX-2 may be involved in the growth and progression of cancer, and this may have prognostic significance. Aim. The aim of our study is to evaluate the expression of COX-2 in colorectal cancer tissue, and to examine the relationship of its expression to various clinicopathological parameters and patient survival. Methods. Formalin-fixed, paraffin-embedded tissue blocks were obtained from 60 patients who underwent surgery for colorectal carcinoma in 1995 at the Chonnam National University Hospital in Gwangju, Korea. We have used an immunohistochemical technique to localize COX-2 in colorectal carcinoma tissues. Results. Immunohistochemical staining of the colorectal cancer specimens demonstrated that COX-2 expression was localized to the carcinoma cells and was not detectable in the stromal compartment of the cancers. The COX-2 immunostaining pattern was predominantly homogenous, and perinuclear cytoplasmic within the tumors. Normal colonic epithelium adjacent to the tumor showed no staining for COX-2. The COX-2 protein was detected in 70% (42/60) of colorectal carcinoma tissues. However, no significant correlation was found between COX-2 expression and various clinicopathological parameters, including histologic grade, tumor size, depth of invasion, lymph node metastasis, distant metastasis, or stage. Furthermore, COX-2 expression did not correlate with patient survival (p=0.401). Conclusion. These results suggest that COX-2 expression may play an important role in the evolution of colon carcinogenesis. However, further studies are needed to determine the prognostic relevance of COX-2.     

MUC2在胃癌及癌前病变中的表达及其意义

目的探讨粘蛋白MUC2在胃癌，癌前病变中的表达及其与胃癌临床病理特征的关系。方法采用免疫组织化学SP法检测10例正常胃粘膜，20例胃炎肠化生组织及49例胃癌组织中MUC2的表达。结果MUC2在正常胃粘膜中没有表达，MUC2在胃炎肠化生粘膜中的表达率为85%，在胃癌中的表达率为73.5%，肠化生粘膜和胃癌组织的阳性率明显高于正常胃粘膜，差异有非常显著性意义（P〈0.001）。MUC2与胃癌的病理组织分型密切相关，高中分化腺癌，低分化腺癌，粘液腺癌的阳性率分别为81.0%，52.6%、100%。差异有显著性（P〈0.05），粘膜腺癌的强阳性表达率为77.8%，与另外两种组织学分型之间有非常显著性差异（P〈0.001）。结论MUC2是胃癌发生发展中的重要因子。MUC2在不同的组织学类型的胃癌中表达不同，粘液腺癌中表达最强。     

贲门癌组织中sPLA2（Ⅱa）的表达

目的探讨河南贲门癌高发区贲门癌组织中sPLA2（Ⅱa）的表达。方法采用免疫组化卵白素-生物素-过氧化物酶复合物（ABC）法分析80例贲门癌组织和16例贲门癌旁肠化组织中sPLA2（Ⅱa）的表达情况：结果sPLA2（Ⅱa）在癌旁肠化组织中的表达高于贲门腺癌组织（75．0％US37．5％，P〈0．05），高、中、低分化贲门腺癌sPLA2（Ⅱa）阳性率分别为38、5％、27．6％、48．0％，三组表达率差异无统计学意义（P〉0．05）。结论sPLA2（Ⅱa）可能参与了贲门癌的癌变过程。     

Helicobacter pylori infection induces a reversible expression of the CDX2 transcription factor protein in human gastric epithelium

Objective. The homeobox gene CDX2 is implicated in the appearance of intestinal metaplasia in Helicobacter pylori gastritis. The aim of this study was to investigate whether CDX2 expression in gastric mucosa occurs before the appearance of overt intestinal metaplasia in H. pylori gastritis, and whether or not this expression is reversible. Material and methods. CDX2 was studied by immunohistochemistry in a cohort of 38 patients with H. pylori gastritis before and after eradication (mean follow-up 6.3 years) of H. pylori. A cohort of 49 individuals with healthy stomachs was analysed as a control. Results. In the control group no immunostaining of CDX2 in the epithelial cells of the gastric body was found, while in 57% of the cases a mild, aberrant nuclear immunostaining of CDX2 in the non-metaplastic epithelial cells in antrum, designated as “positive staining of single cells” (PSSC), was found. In H. pylori gastritis, the PSSC was seen in antrum and corpus in 100% and 26% of the cases, respectively. The prevalence of antral PSSC was significantly increased (on average by 4-fold) in H. pylori gastritis as compared with controls. After eradication of H. pylori, the prevalence of PSSC decreased significantly in antrum but not in corpus. Conclusions. Expression of CDX2 at low intensity is common in the epithelium of normal antrum, and this expression is enhanced in H. pylori gastritis. Expression of CDX2 is reversible at least in antrum after eradication of H. pylori infection.