Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation

AIMS: Changes in the histochemical characteristics of the surface epithelial mucins is the hallmark of Barrett's metaplasia. The study investigated the pattern of expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma as possible indicators of increased malignant potential. METHODS AND RESULTS: Tissue sections from 51 patients with Barrett's intestinal metaplasia, nine with dysplasia (three indefinite) and 28 resected adenocarcinomas were stained with monoclonal antibodies to MUC1 and MUC2. The majority of the patients were men (70/88, 80%) who were treated over a period of 3 years. None of the patients with dysplasia or carcinoma were under surveillance at the time of presentation. All 51 biopsies with Barrett's metaplasia expressed MUC2 and MUC1 was consistently absent. Neither MUC1 or MUC2 were expressed in the dysplastic epithelium whether in its pure form (6/6) or when associated with carcinoma (26/28) (P < 0.005). Three biopsies which were initially classified as high-grade dysplasia expressed MUC1 and these turned out to be carcinomas on further investigations. MUC1 was also expressed in 12/28 (43%) of the adenocarcinomas and majority of these were poorly differentiated stage 3 tumours (P < 0.05). MUC2 was only positive in mucin-secreting carcinomas (4/28; 14%) irrespective of the tumour stage. CONCLUSION: Despite the large number of patients with Barrett's metaplasia and carcinoma, very few patients presented with dysplasia, implying that Barrett's oesophagus is a silent disease in the community presenting late as carcinoma. The study has demonstrated aberrant expression of MUC2 (an intestinal mucin) in Barrett's metaplasia and this expression is lost when the cells become dysplastic. The lack of MUC1 in dysplastic epithelium and its expression in carcinoma could be utilized as a marker which could differentiate dysplasia from carcinoma in mucosal biopsies. Furthermore, expression of MUC1 in advanced stage oesophageal cancers (as in breast cancer) suggests an unfavourable prognosis.     

糜烂性食管炎、Barrett食管及食管腺癌中SOX2、CDX2的表达及其临床意义

目的探讨CDX2、SOX2在糜烂性食管炎、Barrett食管的3种不同组织类型(胃底型、贲门型、肠化生型)及食管腺癌(esophageal adenocarcinoma,EAC)中的表达及意义。方法采用免疫组化Eli Vision两步法检测CDX2和SOX2在35例贲门组、23例胃底组、14例肠化组、10例糜烂性食管炎组、7例EAC组、10例正常食管下段黏膜中的表达情况。结果 CDX2在肠化组及EAC组中的阳性率均为85.7%,显著高于其他四组(P0.05);CDX2阳性率在贲门组(11.4%)、胃底组(0)、糜烂性食管炎组(0)及正常食管组(0)中的差异无显著性(P0.05)。CDX2在贲门组(75%)及EAC组(66.7%)以(+)为主,差异无统计学意义(P0.05),与肠化组(91.7%)以()为主显著不同(P0.05)。SOX2在Barrett食管三组中的阳性率均为100%,显著高于EAC组(28.6%)(P0.05)。SOX2以(++)表达方式在胃底组(95.7%)及贲门组(74.3%)中差异无统计学意义(P0.05);显著高于肠化组(50%)和EAC组(50%)(P0.05)。SOX2和CDX2的表达在肠化型Barrett食管中呈负相关(P0.05),在贲门组、胃底组、EAC组中无明显相关(P0.05)。结论短段贲门型Barrett食管中CDX2的阳性率不高,可能只是一种柱状上皮化生,与EAC的关系不大;CDX2在鳞状上皮向特殊肠上皮化生转化过程中发挥重要作用,SOX2的沉默促进EAC发生。     

Expression of CD44v5 and -v6 in Barrett's carcinoma is not increased compared to that in nondysplastic Barrett's mucosa

Barrett's adenocarcinoma currently shows the highest increase in the incidence of all malignant tumors. Reliable molecular markers to identify Barrett's patients at risk are still missing. Our own results demonstrate that the expression of CD44v6 correlates with the development of dysplasia in colorectal neoplasms. Therefore, we examined the expression of CD44 variants v5 and v6 in normal esophageal mucosa, non-dysplastic Barrett's mucosa, and Barrett's carcinoma. mRNA from biopsy specimens of patients with Barrett's esophagus (n = 19) or Barrett's carcinoma (n = 15) and patients without esophageal diseases (controls; n = 9) were extracted and used as templates for cDNA synthesis. CD44 variants were detected by RT-PCR with primers hybridizing with CD44 sequences up- and downstream of variable exons. CD44v6 expression was found in 36 of 56 biopsy specimens (64%) of non-dysplastic Barrett's mucosa, in 100% of squamous epithelium, and in none of the gastric mucosa specimens. Eleven of 15 specimens (73%) of Barrett's carcinoma tested positive for v6 expression. The identification of v5 expression did not give additional information. There was no correlation between CD44v5 or -v6 expression and staging or grading of the tumors. Expression of CD44v5 and -v6 seems to be independent of the development of cancer in Barrett's mucosa.     

卵巢浆液性和黏液性肿瘤MUC1、MUC2的表达及其意义

目的探讨卵巢浆液性和黏液性肿瘤中黏蛋白MUC1、MUC2的表达与临床病理特征的相关性。方法免疫组化S—P法检测90例卵巢浆液性和黏液性肿瘤的黏蛋白MUC1、MUC2的表达,并对其中50例恶性病例作生存分析。结果（1）交界性与恶性卵巢肿瘤中黏蛋白MUC1的表达阳性率明显高于良性肿瘤,差异有显著性（P〈0．001）;黏蛋白MUC1与WHO病理分级、FIGO临床分期、大网膜转移显著相关（P〈0．05）。（2）黏蛋白MUC2与组织学类型、WHO病理分级相关（P〈0．05）。（3）黏蛋白MUC1与MUC2呈负相关（P〈0．05）。（4）对50例恶性浆液性和黏液性肿瘤进行的生存分析中,单因素分析显示：WHO病理分级、FIGO临床分期、大网膜转移、MUC1表达程度与预后相关（P〈0．05）,而多因素分析中只有FIGO临床分期、MUC1表达程度具有独立的预后意义（P〈0．05）,Kaplan—Meier生存曲线分析显示,Ⅲ、Ⅳ期较Ⅰ、Ⅱ期生存率差异有显著（P〈0．01）,MUC1阳性组和阴性组生存率差异有显著性（P〈0．01）。结论黏蛋白MUC1、MUC2与恶性卵巢浆液性和黏液性肿瘤的浸润、转移相关,Ⅲ、Ⅳ期肿瘤、MUC1强表达可作为恶性卵巢浆液性和黏液性肿瘤预后不良的可行性指标。     

Expression of MUC2, MUC5AC and MUC6 apomucins in carcinoma, dysplasia and non-dysplastic epithelia of the gallbladder

To date, nine apomucins have been characterized and their expression in malignant and premalignant lesions is under evaluation. The purpose of this study was to characterize immunohistochemically the expression of MUC2 (colonic/ intestinal type), MUC5AC (gastric surface type), and MUC6 (pyloric gland type) apomucins in 55 patients with gallbladder carcinoma (10 with in situ carcinoma, 45 with invasive carcinoma), 20 patients with gallbladder dysplasia, and 15 patients with non-dysplastic gallbladder. MUC2 was expressed mainly in 'goblet type' cells. The frequency was increased in non-dysplastic gallbladder (47%), dysplasia (75%), and in situ carcinoma (100%), and decreased in invasive carcinoma (58%). Carcinoma cells expressing MUC2, which were usually distributed at superficial areas, and well-differentiated carcinoma expressed MUC2 more extensively than moderately and poorly differentiated ones. MUC5AC was frequently expressed in gallbladder irrespective of non-dysplastic epithelia, dysplasia and carcinoma. MUC5AC was expressed also in carcinoma cells at deeply invasive sites. MUC6 was expressed frequently in pseudopyloric gland metaplasia as well as dysplasia and carcinoma. In conclusion, non-dysplastic gallbladder has a similar phenotype to gastric pyloric mucosa. Gallbladder carcinoma exhibits both intestinal and gastric surface phenotypes in the early stage of carcinogenesis, with the gastric surface phenotype dominant in invasive carcinoma.     

同源异型盒基因CDX1和CDX2使食管腺癌细胞恶性降低

目的探讨同源异型盒基因CDX1和CDX2对食管腺癌细胞表型的影响。方法用携带人CDX1或CDX2的表达载体转染食管腺癌细胞系SEG-1,观察形态、生长率变化、分裂指数、致瘤性等。结果CDX1或CDX2单独作用都使SEG-1出现类腺样生长排列、生长率下降、分裂指数降低、致瘤性减弱,CDX2的作用大于CDX1。结论CDX1和CDX2均能促进食管腺癌细胞SEG-1分化,减低其恶性。     

CDX1 and CDX2 expression in intestinal metaplasia, dysplasia and gastric cancer

Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.     

Controversies of the cardiac mucosa and Barrett's oesophagus

Confusion regarding the diagnosis of Barrett's oesophagus exists because of a false dogma that cardiac mucosa is normally present in the gastro-oesophageal junctional region. Recent data indicate that the only normal epithelia in the oesophagus and proximal stomach are squamous epithelium and gastric oxyntic mucosa. When this fact is recognized, it becomes easy to develop precise histological definitions for the normal state (presence of only squamous and oxyntic mucosa), metaplastic oesophageal columnar epithelium (cardiac mucosa with and without intestinal metaplasia, and oxynto-cardiac mucosa), the gastro-oesophageal junction (the proximal limit of gastric oxyntic mucosa), the oesophagus (that part of the foregut lined by squamous and metaplastic columnar epithelium), reflux disease (the presence of metaplastic columnar epithelium), and Barrett's oesophagus (cardiac mucosa with intestinal metaplasia). It is also possible to assess accurately the severity of reflux which is directly proportional to the amount of metaplastic columnar epithelium, and the risk of adenocarcinoma which is related to the amount of dysplasia in intestinal metaplastic epithelium present within the columnar lined segment of the oesophagus. Histopathological precision cannot be matched by any other modality and can convert the confusion that exists regarding diagnosis of Barrett's oesophagus to complete lucidity in a manner that is simple, accurate, and reproducible.     

Expression of MUC1 and MUC2 mucins in gastric carcinomas: their relationship with clinicopathologic parameters and prognosis

The aim of this study was to investigate the relationship between MUC1 and MUC2 mucin expressions and clinicopathologic variables in gastric carcinomas with regard to survival times. MUC1 and MUC2 expressions were revealed immunohistochemically in 143 gastric carcinomas. Of these 143 patients, follow-up data were available for 45 (median survival time of 30 months, ranging from 2 to 80 months). MUC1 was detected in 82 (58%), and MUC2 in 60 (42%) out of 143 cases. Papillary adenocarcinomas showed significantly higher MUC1 and MUC2 immunoreactivity than did signet-ring cell and mucinous tumors (p = 0.045 and p = 0.01, respectively). MUC1 was highly positive in intestinal-type carcinomas (p = 0.006), whereas intestinal and diffuse carcinomas did not differ in MUC2 expression. There was a positive correlation between tumor differentiation and MUC1 expression. However, no correlation was found between MUC1 and MUC2 expressions and angiolymphatic invasion. According to the TNM classification, stage 1A tumors have significantly lower rates of MUC1 reactivity compared to higher stages (p = 0.04). The patients with gastric carcinomas expressing MUC1 showed significantly poorer survival than those without MUC1 expression (p = 0.04). The present study suggests that MUC1 expression be a useful prognostic factor for predicting the outcome of gastric carcinoma patients, whereas the role of MUC2 expression is still unclear.     

MUC1, MUC2 and MUC5AC expressions in cardiac myxoma

Background Cardiac myxoma, the most common primary tumor of the heart, has a variable clinical presentation and immunohistochemical profile. An abundant mucopolysaccharidic matrix exists, including mucin, within cardiac myxoma. This investigation first reports the expressions of mucin genes in cardiac myxoma.Methods A retrospective study was conducted between December 1976 and February 2003, comprising 101 consecutive patients with cardiac myxoma who were treated with surgical excision. Detailed clinical parameters also were reviewed. Mucin genes, namely MUC1, MUC2 and MUC5AC, were studied immunohistochemically in 47 randomly selected patients.Results The study group contained 57 (57%) women and 44 (43%) men, with a mean age of 38±21 years. Their presentations included: asymptomatic (41%), dyspnea (35%), stroke (23%), chest pain (7%), fever (6%), syncope (5%) and tricuspid regurgitation (70%). The sample included 90 myxoma located in the left atrium, 3 (3%) recurrent myxoma and 8 (8%) myxoma not located in the left atrium. The myxoma did not differ with location or clinical event in terms of pathological scores, such as vascular proliferation, inflammation, cellularity, hyaline, calcification and thrombosis. Cardiac myxoma is characterized by excessive mucus secretion. Expression of membrane-associated MUC1 was considerably higher than that of the secreted mucins, MUC2 and MUC5AC (P<0.05). Furthermore, expression of MUC5AC is related to lesser embolism (P<0.05).Conclusions This work first examined the immunohistochemical expression of mucin (MUC1, MUC2 and MUC5AC) in cardiac myxoma. This investigation then showed that the expression of representative membrane-associated mucin, MUC1, and/or secretory mucins, MUC2 and MUC5AC, in cardiac myxoma was associated with important tumor clinicopathological characteristics. Moreover, MUC5AC appears related to lesser embolism. This approach can help distinguish the potential roles of secretory mucins versus membrane-associated mucins in the development of cardiac myxoma.     

消化道癌患者胃肠道粘膜中MUC2和MUC3基因的表达

应用免疫组织化学和原位杂交方法检测人消化道癌患者胃肠道粘膜中的ＭＵＣ２和ＭＵＣ３基因蛋白产物和ｍＲＮＡ的表达，以提示ＭＵＣ２和ＭＵＣ３基因在人消化道癌患者胃肠道粘膜中的表达规律，结果发现，胃粘膜中无ＭＵＣ２和ＭＵＣ３基因产物的表达，ＭＵＣ２核粘蛋白及ｍＲＮＡ主要存在十二指肠和结肠杯状细胞周及核上，柱状细胞中无表达。ＭＵＣ３核粘蛋白及其ｍＲＮＡ主要存在十二指肠和结核的杯状细胞和柱状细胞胞浆内，而杯状     

Expression of MUC1 and MUC2 mucins and relationship with cell proliferative activity in human colorectal neoplasia

Our previous studies on MUC1 and MUC2 mucin expression in various human neoplasms have found that MUC1 expression is related with a poor outcome whereas MUC2 expression is related with a favorable outcome. In the present study, we examined the alteration of MUC1 and MUC2 antigens on malignant transformation of colorectal mucosa, and also its relationship with cell proliferative activity (Ki-67 labeling index) of neoplastic epithelial cells in 200 adenomas and 58 carcinomas. In the 200 adenomas, we analyzed a total of 400 adenomatous lesions (mild dysplasia, 200 lesions; moderate dysplasia, 153 lesions; severe dysplasia, 47 lesions). MUC1 was expressed in carcinomas (24%) and adenomas with severe dysplasia (4%), but was not expressed in adenomas with mild or moderate dysplasia. MUC2 was expressed in a significantly greater number of adenomas with mild dysplasia (72%) than in adenomas with moderate dysplasia (45%) or severe dysplasia (47%), as well as in the carcinomas (38%; P < 0.0001). The Ki-67 labeling index was significantly lower in the MUC2-positive cases than in the MUC2-negative cases in the adenomas with mild dysplasia (13.6 vs 24.2%; P < 0.0001) or moderate dysplasia (25.7 vs 44.4%; P < 0.0001), and in the carcinomas (32.5 vs 48.4%; P < 0.05). In conclusion, the data from our study indicate that increased MUC1 expression and reduced MUC2 expression may be related to malignant transformation of colorectal neoplasia. We also demonstrated that decreased MUC2 expression, which is correlated with increased Ki-67 labeling, may play an important role in the progression of colorectal adenomatous change.     

Expression of CDX2 in benign tissue and adenocarcinoma of the prostate

Numerous studies have claimed that CDX2 is relatively specific and sensitive in establishing a gastrointestinal origin in metastatic tumors of unknown origin. We have recently seen 2 cases of prostatic adenocarcinoma (PCa) on needle biopsies with diffuse strong nuclear staining for CDX2 sent for consultation. One case was a prostatic duct adenocarcinoma in a man with a prostate-specific antigen (PSA) value of 327 ng/mL, and the other was a PCa with a Gleason score (GS) of 4 + 4 = 8 in a man with a PSA value of 15 ng/mL. An adenocarcinoma with GS 3 + 3 = 6 from the contralateral side did not express CDX2. Because documented examples of this phenomenon are rare, we investigated the immunoexpression of CDX2, using tissue microarrays (TMAs). Three slides of TMAs were used to stain 708 tissue samples (0.6 mm in diameter) containing either benign or malignant prostate tissue, as well as control tissues from various anatomical sites including colon. In total, 195 samples of primary PCa with GS of 6 (n = 41), 7 (n = 21), and 8 (n = 8); 195 samples of benign prostate tissue; and 185 samples of metastatic PCa were studied. Of 70 radical prostatectomy specimens examined for PCa in TMAs, 4 (5.7%) were positive for CDX2, showing Gleason score of 6 (n = 3) and Gleason score of 7 (n = 1). Focal moderate positive staining was seen in benign prostate tissue in 7 (11.7%) of 60 radical prostatectomy specimens. None of the metastatic PCa expressed CDX2. CDX2 may uncommonly be focally expressed in benign prostatic glands. Staining in PCa is less common and appears independent of GS and is usually patchy and focal and of lesser intensity than in colonic tissue. However, rarely strong and diffuse staining may be seen. Positive CDX2 staining in high-grade prostate cancer (ductal, cribriform, and solid) may be confused with secondary carcinoma of colonic origin. Routine histopathology, positive PSA immunostaining, and clinical findings can help confirm the correct diagnosis.     

胃癌及癌旁组织中CDX2和claudin-3的表达及其意义

目的探讨CDX2和claudin-3在胃癌及癌旁组织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SP法检测CDX2和claudin-3在67例胃癌及32例癌旁组织中的表达。结果 (1)CDX2在癌旁正常组织中不表达,癌旁肠化上皮的阳性率(87.5%)明显高于胃癌组织(44.8%,P<0.001)。CDX2在Lauren分型肠型胃癌中的阳性率(62.9%)明显高于弥漫型胃癌(25.0%,P<0.05);CDX2表达与胃癌分化程度呈正相关(P<0.05),而与淋巴结转移和TNM分期呈负相关(P<0.05)。claudin-3在胃癌组织中的阳性率(77.6%)明显高于癌旁正常组织(36.7%,P<0.001),胃癌中claudin-3仅与淋巴结转移呈正相关(P<0.05)。(2)5年生存分析显示:CDX2阳性组胃癌5年生存率(76.7%)明显高于阴性组(43.2%,P=0.01)。claudin-3与胃癌患者5年生存率无明显相关性(P>0.05)。根据CDX2和claudin-3在胃癌中联合表达结果进行生存分析,结果显示CDX2+/claudin-3-的胃癌患者,5年生存率最高(P=0.004)。多因素回...     

Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas: its relationship with tumor progression and prognosis

Our previous immunohistochemical studies in the pancreas, intrahepatic bile duct, and ampulla of Vater demonstrated that an invasive carcinoma with a poor outcome showed a pattern of MUC1 (membrane-bound mucin) positive and MUC2 (intestinal-type secretory mucin) negative, whereas many of the non-invasive tumors with favorable outcome showed a pattern of MUC1 negative and MUC2 positive. The aim of this study is to compare the expression profiles of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas to gain insight into the relationship between the biological nature of the carcinomas and the role of mucins. We examined the expression profiles of MUC1 of different glycoforms and MUC2 in 60 extrahepatic bile duct carcinomas using immunohistochemistry.The expression of MUC1/CORE (core peptide of MUC1), MUC1/DF3 (core peptide of MUC1 with sialyl oligosaccharides) and MUC1/MY.1 E12 (sialylated MUC1) showed a significant relationship with tumor progression factors such as poor differentiation, deep invasion, lymph node metastasis, lymphatic invasion or perineural invasion. In contrast, the expression of MUC1/HMFG-1 (fully glycosylated MUC1) did not show a significant relationship with the tumor progression factors. In the different glycoforms of MUC1 examined, the expression of MUC1/DF3 and MUC1/MY.1E12 was related with the poor outcome of the patients. In contrast, the expression of MUC2 was inversely related with the tumor progression factors and poor outcome. In the 52 patients with advanced tumors, only MUC1/DF3 high expression correlated with poor prognosis. In conclusion, MUC1/DF3 was the most useful prognosis indicator among the various glycoforms of MUC1 mucins.     

CDX2和CYP24A1在大肠癌中的表达

目的 通过研究CDX2、CYP24A1在大肠癌中的表达研究,探讨CDX2和CYP24A1的相关性。方法 应用免疫组化S-P法检测100例大肠癌组织及20例正常大肠癌组织中CDX2和CYP24A1的表达。结果 大肠癌组织中的CDX2和CYP24A1的蛋白表达低于正常大肠癌组织中的表达（P<0.05）, 以正常大肠组织作为对照,CDX2 的蛋白水平表达量为100.00%, 癌旁组织和大肠癌组织的 CDX2 蛋白的相对表达量分别为77.12%、46.65%。CYP24A1 的蛋白水平表达量为 43.81%, 癌旁组织和大肠癌组织的 CYP24A1 蛋白的相对表达量分别为75.00%、96.82%。通过Pearson相关分析显示CDX2蛋白表达水平与CYP24A1蛋白表达水平之间呈显著负相关关系（P<0.05）。结论 CDX2和CYP24A1是具有较高敏感性的肠上皮特异性标志物,联合检测CDX2和CYP24A1的表达有助于鉴别良恶性大肠肿瘤。     

Expression of MUC1 and MUC2 mucin core proteins and their messenger RNA in gall bladder carcinoma: an immunohistochemical and in situ hybridization study

Expression of mucin core protein MUC1 and MUC2 was examined at the protein and mRNA level in 55 cases of carcinoma and 20 of dysplasia, and in 15 non-dysplastic epithelia of the gall bladder. In non-dysplastic epithelium, MUC1 protein was not expressed, while in dysplasia, MUC1 was focally expressed in ten cases, particularly in those associated with carcinoma. In carcinoma, MUC1 was expressed heterogeneously, and the frequency and extent of MUC1 expression increased with histological dedifferentiation. MUC1 was found on the apical cell surface and also in the cytoplasm in well- and moderately-differentiated carcinoma, and on the cell border in poorly-differentiated cases. In infiltrative regions, MUC1 expression was more predominant and MUC1 frequently leaked outside the foci of carcinoma. By contrast, MUC2 was focally expressed in non-dysplastic as well as in dysplastic epithelia and more frequently in well-differentiated adenocarcinoma. MUC2-positive cells resembled goblet cells, whether in non-dysplastic epithelium, dysplasia or carcinoma. Cell proliferative activity was higher in MUC1-positive than in MUC1-negative carcinoma cells. Distributions of MUC1 and MUC2 mRNA signals and of MUC1 and MUC2 proteins were similar in carcinoma and dysplasia. These results suggest that MUC1 expression by gall bladder carcinoma may reflect histological dedifferentiation, increased proliferative activity, and invasiveness, while MUC2 expression is related to lower proliferative activity and reflects some differentiation towards goblet cells; and that MUC1 expression in gall bladder dysplasia reflects malignant transformation. Copyright © 1999 John Wiley & Sons, Ltd.     

CDX2和Villin在胃黏膜病变中的表达及其临床病理意义

目的:探讨CDX2和Villin在胃黏膜病变中的表达及其临床病理意义和诊断作用.方法:收集2015年1月至2017年5月本院胃黏膜活检标本90例,其中慢性胃炎21例,慢性胃病伴肠上皮化生22例,胃上皮内瘤变25例,胃癌22例.采用免疫组织化学方法检测CDX2和Villin蛋白在胃黏膜活检组织中的表达.结果:CDX2及Villin在慢性胃病伴肠上皮化生组、胃上皮内瘤变组及胃癌组均有高表达,其阳性率显著高于慢性胃炎组,差异有统计学意义(P<0.01);CDX2与Villin的表达存在正相关(P<0.01).结论:CDX2和Villin异常表达于胃黏膜肠上皮化生、胃上皮内瘤变及胃癌组织中,提示两者可能在胃癌(特别是肠型胃癌)的发生中起重要意义,同时在胃黏膜活检中诊断胃癌及癌前病变(尤其是形态学难以确定)时,两者联合检测可以作为辅助诊断的依据.     

Expression and significance of CDX2, FXR,and TGR5 in esophageal cancer

This study explored the expression and significance of three critical morphogenesis genes in normal esophagus, reflux esophagitis (RE), Barrett’s esophagus (BE), esophageal adenocarcinoma (EA), and esophageal squamous cell carcinoma (ESCC). Esophageal tissue samples and tissue microarrays were used. CDX2, FXR, and TGR5 protein expression were measured by immunohistochemistry in normal esophageal, RE, BE, EA, and ESCC tissues. All 3 proteins had markedly changed expression during the progression of EA. The expressions of CDX2 and FXR were positively correlated in EA. In addition, TGR5 expression was positively correlated with CDX2 in RE and BE. The expressions of CDX2 and FXR were also positively correlated in ESCC. Although CDX2, FXR, and TGR5 were upregulated in ESCC, these factors might not be markers for the prognosis of ESCC. These results suggested that CDX2, FXR, and TGR5 might play different roles in EA and ESCC. They may represent novel therapeutic targets for patients with these cancers.