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。     

CDX2在肝外胆管癌中的表达意义及其与Ki-67的相关性

目的：探讨肝外胆管癌中CDX2的表达,及其与临床病理特征、Ki-67增殖指数之间的相关性。方法应用免疫组化MaxVision法检测40例肝外胆管癌以及10例非癌胆管组织中CDX2与Ki-67的表达。结果40例肝外胆管癌中CDX2阳性率(35%,14/40)高于非癌胆管组织(10%,1/10)(P<0．05),CDX2表达与肿瘤分化程度具有相关性(χ2=6．411,P<0．05)。 CDX2与Ki-67的表达呈负相关( rs =-0．645,P<0．05)。结论 CDX2可能在肝外胆管癌的发生、发展中发挥作用,其不仅参与肿瘤细胞的分化,也可能通过某种机制调控细胞的增殖。     

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.     

转录因子CDX2过表达对人胃癌SGC-7901细胞增殖和细胞周期的影响*

 目的： 探索CDX2过表达对人胃癌SGC-7901细胞增殖、生长和细胞周期的影响及其分子机制。方法: 采用携带CDX2基因的重组慢病毒颗粒（LV-CDX2-GFP）感染SGC-7901细胞,作为实验组（LV-CDX2-GFP组）;以对照慢病毒颗粒（LV-GFP）感染SGC-7901细胞,作为阴性对照组（LV-GFP组）;空白对照组常规培养,不做任何处理。分别采用CCK-8法检测细胞的增殖活力,流式细胞术检测各组细胞周期的分布,半定量逆转录-聚合酶链反应（RT-PCR）和Western blotting技术检测细胞中CDX2、Bax、Bcl-2、cyclin D1和survivin mRNA和蛋白的表达。结果: 与LV-GFP组和空白对照组比较,LV-CDX2-GFP组细胞增殖活力明显降低(P<0.05),G0/G1期所占比例上升(P<0.05),Bcl-2、cyclin D1和survivin mRNA和蛋白的表达降低（P<0.05）,Bax mRNA和蛋白的表达上调（P<0.05）,而LV-GFP组与空白对照组比较,差异无统计学意义（P>0.05）。结论: 慢病毒介导的CDX2过表达抑制胃癌细胞增殖和生长,使细胞周期停滞在 G0/G1期,其机制可能与CDX2过表达使胃癌细胞Bcl-2、cyclin D1、survivin表达下调和Bax表达上调有关。     

探讨CDX2在胃肠道腺癌诊断中的病理学价值

目的观察CDX2在多种正常组织和肿瘤组织中的表达特点,探讨CDX2在胃肠道腺癌诊断中的病理学价值。方法采用组织芯片和免疫组织化学（EliVision）方法,对CDX2在76例正常组织和612例肿瘤组织（结肠癌、胃癌、肝癌、前列腺癌、肾细胞癌、乳腺癌、肾上腺腺癌、淋巴瘤、肺癌等）中的表达特点进行分析。结果CDX2在13例正常肠道上皮、8例胰腺小导管上皮中呈强阳性表达;在47例（92．2％）结肠腺癌组织、58例（66．9％）胃癌组织中呈强阳性表达;在其他少数肿瘤组织中呈弱阳性或散在阳性,其阳性率分别是卵巢黏液癌10／64、胰腺肿瘤3／9、甲状腺癌3／11、肝外胆道系统肿瘤4／16;在乳腺、前列腺、肾、肾上腺、肝等正常组织和肿瘤组织中未见CDX2表达。结论CDX2主要在正常肠道、胰腺小导管上皮和胃肠道肿瘤中表达,少数其他部位的上皮性肿瘤也有CDX2的表达,但表达特点与在胃肠道肿瘤不同。因此CDX2在鉴别原发癌和转移癌时具有一定的参考价值。     

结直肠肿瘤的新标记——CDX2

CDX2是一种新发现的特异性的核转录因子，对正常和肿瘤性的肠上皮均有相对特异性和敏感性，用它作免疫组织化学染色可以用来诊断胃肠道起源的肿瘤以及辅助明确转移性肿瘤是否来源于肠道。目前与它相对应的常用的抗体是CDX2－88，它是一种单克隆抗体（小鼠IgG1、k抗体）。本文就CDX2与结直肠肿瘤关系的研究及应用作一综述。     

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。     

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...     

贲门三源性碰撞瘤1例并文献复习

目的观察食管胃交界处三源性碰撞瘤的临床病理学特征,初步探讨其病理诊断标准、发病机制、常规病理镜下形态、免疫表型及预后。方法回顾性分析1例贲门三源性碰撞瘤的临床病理学特征及免疫表型,并复习相关文献。结果眼观:食管及近端胃切除标本,食管胃交界处见一溃疡型肿物;肿瘤由食管延续至胃黏膜小弯侧,侵犯食管壁及胃壁全层。镜检:贲门溃疡型肿物由三种完全不同类型的组织学成分构成,包括高分化鳞形细胞癌、神经内分泌肿瘤(G3)及中分化腺癌,三者分界清楚,且三种肿瘤成分均发生淋巴结转移。免疫表型:肿瘤的三种成分中,鳞状细胞癌成分表达p40、p63、CK5/6,Ki-67增殖指数为30%,p53阳性率为60%;神经内分泌癌成分表达CgA、Syn、CD56;腺癌成分表达CK7;神经内分泌癌与腺癌成分均表达CDX2和Villin,且两者Ki-67增殖指数均为40%,p53阳性率均为80%。结论目前食管胃交界处三源性碰撞瘤的诊断主要依赖组织形态学及免疫表型;根据碰撞瘤中各种肿瘤成分不同的侵犯及转移程度,并结合其他肿瘤诊断相关指标,对患者行个体化治疗。     

SATB2在卵巢转移性Krukenberg瘤诊断中的应用价值:70例与CDX2、CK7、CK20、CgA、Syn免疫组化对比性研究

正SATB2是结直肠腺癌的敏感指标之一,目前尚未发现其在卵巢转移性Krukenberg瘤(MKTs)诊断中应用价值的研究。作者对70例来源于不同器官:胃27例,结直肠13例,阑尾20例包括19例除外杯状细胞类癌的转移性腺癌(AdexG CC)和1例具有印戒细胞特征的传统型差分化癌,乳腺5例,膀胱3例,肺2例的MKTs行SATB2免疫组化染色,评估其诊断价值。作者对比分析了SATB2与CDX2、CK7、CK20、CgA、Syn     

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.     

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.     

Expression of CDX2 and MUC2 in Barrett's mucosa

Barrett's mucosa is a risk factor for esophageal adenocarcinoma and should be detected at an early stage. It is defined by the presence of columnar epithelium with goblet cells in the lower esophagus, but histologic diagnosis can be uncertain in the absence of distinct goblet cells. We investigated 55 biopsies from 48 patients with endoscopically plain Barrett's esophagus and performed immunohistochemistry for CDX2 and MUC2. In addition, alcian blue (pH 2,5)/PAS staining was done. In histologically unequivocal Barrett's mucosa, nuclear expression of CDX2 in goblet cells and many columnar cells, as well as cytoplasmic positivity for MUC2 in goblet cells, could be observed. Alcian blue (pH 2,5)/PAS stained acidic mucins in goblet cells and in some non-goblet columnar cells. In six cases, no definite Barrett's mucosa was present, and no expression of MUC2 could be observed. In these biopsies, there was granular cytoplasmic and/or focal nuclear staining for CDX2 in non-goblet columnar epithelial cells, indicating their intestinal differentiation. We suggest that this peculiar mucosa is the precursor of unequivocal Barrett's mucosa and would designate it early Barrett's mucosa. Alcian blue for acidic mucins is inconsistent in this epithelium and does not reliably indicate early intestinal differentiation.     

SATB2 is a supplementary immunohistochemical marker to CDX2 in the diagnosis of colorectal carcinoma metastasis in an unknown primary

CDX2 is routinely used for identifying gastrointestinal origin of metastatic adenocarcinomas; but a high percentage of other carcinomas also show positivity with this antibody. SATB2 is a new immunohistochemical marker with a few studies showing that it is specifically expressed in a large majority of colorectal adenocarcinomas. We assessed SATB2 along with CDX2 in patient material with metastasis in order to determine whether the primary site could be identified as ‘colon‐rectum’. Metastasis in 67 liver biopsies, 108 lymph nodes from resection specimens and 36 serous effusions was analyzed retrospectively. Blinded slides stained for CDX2 and SATB2 were assessed individually by two pathologists and sensitivity, specificity and kappa statistics were calculated. Sensitivity for CDX2 in metastasis from colorectal adenocarcinomas was 93%; while in SATB2 it was 79%. The combination of CDX2 and SATB2 yielded a sensitivity of 79% and a high specificity of 93%. There was an acceptable level of agreement (κ = 0.64) between the pathologists for both the markers in case of colorectal adenocarcinoma metastasis. CDX2 is a sensitive marker compared to SATB2; while the specificity of combination of CDX2 and SATB2 is high for metastasis from colorectal adenocarcinoma. SATB2 can be used as a supplementary marker along with CDX2 to identify colorectal origin for material received from patients clinically presenting with metastasis.     

CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach

CDX2 and liver-intestine (LI)-cadherin are intestine-specific markers and both are physiologically expressed in the small intestine and colon. Recent studies have demonstrated that CDX2 regulates LI-cadherin gene (CDH17) expression in colorectal cancer. The present study investigated the relationship of CDX2 and LI-cadherin expression in gastric cancer. One hundred and nine pairs of tumour and non-cancerous gastric mucosa were collected from gastrectomy specimens. Protein expression levels of CDX2 and LI-cadherin were determined by immunohistochemical staining. Semi-quantitative RT-PCR showed that the mRNAs of both CDX2 and CDH17 were highly expressed in tumour compared with non-cancerous mucosa. Overexpression of CDX2 was significantly associated with CDH17 in gastric adenocarcinoma. Furthermore, the expression of CDX2 and LI-cadherin proteins was strongly coupled in intestinal metaplasia. In conclusion, overexpression of CDH17 is significantly associated with CDX2.