Morules with optically clear nuclei in ovarian borderline endometrioid tumor

Optically clear nuclei (OCN) have been observed in morules of some neoplasms and in some conditions unrelated to the development of the morules. We first report a case of ovarian borderline endometrioid tumor (BET) showing the morules associated with OCN. The patient was a 47-year-old premenopausal woman with a left ovarian cystic tumor, atypical endometrial hyperplasia, and elevated serum levels of FSH, LH, estradiol, and CA 125. The resected ovarian tumor measured 6 cm in diameter, and showed a papillary growth. Histologically, the ovarian tumor was consistent with BET, and the morules with OCN were scattered. Immunohistochemically, OCN were proven to be rich in biotin. An aberrant nuclear expression of beta-catenin was observed in both the tumor cells and the morular cells. Our case may suggest the possibility that the appearance of OCN with or without morules in ovarian tumors is related to endometrioid differentiation of the tumor cells, and should be recognized as a diagnostic clue of ovarian endometrioid tumors. Although female sex hormones have been reported to play a role in the occurrence of OCN, the participation of beta-catenin mutation has also been suggested.     

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.     

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.     

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。     

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...     

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.     

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。     

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 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.     

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.