Cytokeratin polypeptide in gastrointestinal adenocarcinomas displaying squamous differentiation.

In the present study we investigated the cytokeratin (CK) polypeptide expression in gastric and colonic adenocarcinomas. A battery of monoclonal anti-cytokeratin-specific antibodies and anti-vimentin were used. While the majority of cases displayed simple epithelial characteristics, in three of 17 cases of gastric adenocarcinomas and in one of 20 cases of colonic adenocarcinomas, CK polypeptides 13 (54 kd) and 16 (48 kd) were occasionally detected. These CK polypeptides, characteristic of squamous nonkeratinizing epithelia, were found in cases in which no evidence of squamous differentiation could be demonstrated by histologic examination. We believe that the presence of these unique CK polypeptides points to the squamous differentiation potential of the tumor cells.     

The activated nerve growth factor receptor p-TrkA is selectively expressed in advanced-stage ovarian carcinoma

The objective of this study was to compare the expression of the nerve growth factor (NGF) receptors TrkA and p75 in ovarian borderline tumors, International Federation of Gynecology and Obstetrics (FIGO) stage I carcinomas and advanced-stage (FIGO stage III-IV) carcinomas, and to assess a possible association between NGF receptor expression and mitogen-activated protein kinase (MAPK) activation in borderline tumors and FIGO stage I carcinomas. Sections from 119 borderline tumors, 57 FIGO stage I invasive ovarian carcinomas, and 56 advanced-stage carcinomas were evaluated for expression of activated phospho-TrkA (p-TrkA) and p75 using immunohistochemistry. MAPK activation was analyzed in stage I carcinomas and borderline tumors using phospho-specific antibodies against the extracellular-regulated kinase (p-ERK), the high osmolarity glycerol response kinase (p-p38), and the c-jun amino-terminal kinase (p-JNK). p-TrkA membrane expression was significantly more frequent in advanced-stage carcinomas compared with both borderline and stage I carcinomas (P < .001). p75 membrane expression was comparable in the 3 groups (P > .05). p-ERK and p-p38 expression was comparable in borderline and stage I carcinomas, whereas p-JNK was more frequently expressed in stage I ovarian carcinomas (P < .001). NGF receptor expression showed no association with MAPK activation in borderline and stage I carcinomas. In conclusion, expression of biologically active p-TrkA receptor at the cell membrane is up-regulated along tumor progression in ovarian carcinoma, whereas p75 expression remains unaltered. These data provide further evidence regarding the clinical role of p-TrkA in ovarian carcinoma. NGF receptors probably signal via MAPK-independent pathways in ovarian carcinoma.     

CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer.

Intestinal metaplasia is a key event in multistep gastric carcinogenesis. CDX2, a master regulator of intestinal phenotype, was shown to play a tumor-suppressive role in colon cancer. However, it was reported to be expressed in nearly all gastric intestinal metaplasia and many gastric cancers. As CDX2 is differentially expressed in normal stomach and intestine, we sought to relate the CDX2 expression to gastrointestinal differentiation along gastric carcinogenesis. The expression of CDX2 protein in gastric intestinal metaplasia, dysplasia and cancer was examined and related to their gastrointestinal differentiation. CDX2 expression was significantly decreased in incomplete intestinal metaplasia, which expresses both gastric mucins (MUC5AC and MUC6) and intestinal mucin (MUC2), compared with complete intestinal metaplasia, which expresses intestinal mucin (MUC2) only. Although incomplete intestinal metaplasia morphologically resembles colon, its CDX2 expression was apparently lower than that in the normal colon. Moreover, CDX2 expression was progressively reduced in gastric dysplasia and cancer. The CDX2 expression in gastric cancer was also inversely correlated with the expression of gastric mucins. As incomplete intestinal metaplasia is associated with higher risk of gastric cancer, its lower CDX2 expression compared with that in complete intestinal metaplasia and normal colon epithelium resolved the current contradiction between the tumor-suppressive role of CDX2 in the colon and the high prevalence of CDX2 in intestinal metaplasia. Further decrease of CDX2 expression in gastric dysplasia and cancer suggests that CDX2 plays a similar anticarcinogenic role in intestinal metaplasia as it does in colon. Intestinal metaplasia or dysplasia with low expression of CDX2 may serve as predictive markers for gastric cancer.     

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.     

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。     

Phenotypic expression of gastrointestinal differentiation markers in colorectal adenocarcinomas with liver metastasis

AIM: The purpose of the present study was to clarify the correlation between phenotypic expression of gastrointestinal differentiation markers and colorectal cancer behaviour, particularly invasion and hepatic metastasis. METHODS: Thirty-one cases of advanced colorectal adenocarcinoma (CRC) with liver metastasis were selected. Phenotypic patterns were evaluated immunohistochemically by means of antibodies to CD10, MUC2, and human gastric mucin (HGM). RESULTS: The incidence of MUC2 (45.2%) and HGM (16.1%) expression in CRCs with liver metastasis did not differ from non-metastatic CRCs. In contrast, the incidence of CD10 expression was significantly higher in CRCs with liver metastasis (58.1%) than in control CRCs (21.7%). Phenotypic expression in the liver metastasis carcinomas was similar to that of the primary lesions. CONCLUSIONS: The findings suggest that cases of CRC with CD10 expression are at increased risk of liver metastasis. Even if there is no liver metastasis at laparotomy for CRC, careful follow-up is recommended for CRCs with CD10 expression.     

VEGFR2 is selectively expressed by FOXP3high CD4+ Treg

CD25⁺ FOXP3⁺CD4⁺ T cells (Treg) have been considered to play an important role in immune tolerance against several tumor antigens. It has also been indicated that high‐level expression of FOXP3 (FOXP3^high) is sufficient to confer suppressive activity to normal non‐Treg. Here, we showed for the first time that vascular endothelial growth factor receptor 2 (VEGFR2) is selectively expressed by FOXP3^high but not FOXP3^low Treg. Such VEGFR2⁺ Treg exist in several tissues including PBMC and malignant effusion‐derived lymphocytes. In conclusion, VEGFR2 may be a novel target for controlling Treg with highly suppressive function.