Fascin expression in human embryonic, fetal, and normal adult tissue.

This study investigates the distribution of fascin in human embryonic, fetal, and normal adult tissues. Tissue microarray technology was used to perform immunohistochemical experiments on human embryos and fetuses at 4-22 weeks of gestation and adult specimens. Fascin was widely expressed in the nervous system. At 4 weeks of gestation, fascin was present in the neural tube. At 8-12 weeks of gestation, homogenous gene expression was seen in cells of the cerebellum and gastrointestinal tract. In later developmental stages and in adults, Purkinje cells of the cerebellum and glandular epithelium of the gastrointestinal tract showed no expression. Fascin was expressed in the cortex and medulla of the adrenal gland at 8-12 weeks of gestation, whereas immunoreactivity decreased from the zona glomerulosa through the zona reticularis and was essentially negative in the adrenal medulla of adults. Significant expression of fascin was seen throughout development in neurons, follicular dendritic cells of lymphoid tissue, basal layer cells of stratified squamous epithelia, mesenchyme, and vascular endothelial cells. Simple columnar epithelia of the biliary duct, colon, ovary, pancreas, and stomach were all negative for fascin expression. These results show that expression of fascin is time specific and highly tissue specific. Parallels between fascin expression in embryogenesis and carcinogenesis are discussed.

Expression of fascin in thyroid neoplasms: a novel diagnostic marker.

PURPOSE: Fascin, an actin-bundling protein, is markedly upregulated in several epithelial tumors and its expression often correlates with high-grade, extensive invasion, and distant metastasis. However, reports about fascin expression in endocrine tumors remain rare. The aim of the present study was to assess the diagnostic significance of fascin in thyroid neoplasms. METHODS: Thyroid samples from 177 cases were examined for fascin and Ki-67 expression by immunohistochemistry. RESULTS: Fascin immunoreactivity was negative in normal follicles and nodular goiter. Fascin immunostaining was positive in 62.1% (41/66) of thyroid carcinomas and 26.4% (19/72) of thyroid adenomas; the difference being significant (P < 0.0001). In thyroid papillary carcinoma, upregulation of fascin was associated with both the Ki-67 labeling index and the occurrence of lymph node metastasis. CONCLUSION: Fascin may be a novel marker to distinguish thyroid carcinoma from benign lesions and may be involved in the proliferation and metastasis of papillary carcinoma.

Regulation of neutrophil gelatinase-associated lipocalin expression by C/EBPß in lung carcinoma cells.

Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin family, has been found to be overexpressed in a variety of tumors, including lung adenocarcinomas. However, the mechanism by which NGAL expression is regulated in lung carcinoma needs further evaluation. In this study, immunohistochemistry was employed to analyze the expression of NGAL in lung carcinoma tissue samples, including lung squamous carcinomas, adenocarcinomas, adenosquamous carcinomas and bronchial alveolar cell carcinomas. The results showed that NGAL was expressed in 82.61% (19/23) of the samples. RT-PCR and immunofluorescent staining showed that NGAL was localized to the cytoplasm in lung carcinoma cell lines. To explore the transcriptional regulation mechanism of NGAL basal expression in lung carcinoma, a 1515-bp fragment (-1431 to +84) of the NGAL promoter region was cloned and a series of deletion and mutation constructs were generated. These constructs were analyzed using the luciferase reporter assay. The results indicated that the cis-acting elements important for the basal activity of NGAL transcription were likely located between -152 and -141. Further analysis using site-directed mutagenesis and the luciferase reporter assay suggested that the C/EBP binding sites were responsible for the activity of the NGAL promoter. Finally, the binding ability and specificity of the transcription factors were determined by electrophoretic mobility-shift assay (EMSA). The results showed that C/EBPß was able to bind to the -152 and -141 segments. Taken together, these findings suggest that NGAL is expressed in lung carcinomas and that NGAL expression is mediated by the binding of C/EBPß to the -152 and -141 segment of the NGAL promoter.

Expression of NGAL and NGALR in human embryonic, fetal and normal adult tissues.

This study investigated the distribution of neutrophil gelatinase-associated lipocalin (NGAL) and neutrophil gelatinase-associated lipocalin receptor (NGALR) in human embryonic, fetal and normal adult tissues. Tissue microarray technology was used to perform immunohistochemical examination on human embryos, fetuses at 4-22 weeks of gestation and adult tissue specimens. Results demonstrated that during the development of the nervous system, NGALR was prevalent in the neural tube and cerebrum, and NGAL was only detected in the stellate cells of the cerebrum and the Purkinje cells of the cerebellum. NGAL and NGALR were expressed in the lung alveolar epithelium and in the gastrointestinal tract in embryos, but were almost undetectable in later developmental stages. In the embryonic adrenal glands, the two proteins demonstrated moderate positivity in the cortex and the medulla. In adults, NGAL was particularly present in the cells of the inner and outer layers of the cortex and was absent in the medulla, while NGALR exhibited strong positivity in the cortex and the medulla. Evident expression of NGAL and NGALR was observed throughout development in the neutrophil-rich sites, the renal tubule epithelium and certain gland epithelia of the gastrointestinal tract, but was undetectable in the heart, liver and thyroid gland. Taken together, these results demonstrated that the expression of NGAL and NGALR was time-specific and highly tissue­specific. Correlations between their expression in embryogenesis and carcinogenesis should be examined.

Expression of ezrin in human embryonic, fetal, and normal adult tissues.

Ezrin, which cross-links the cytoskeleton and plasma membrane, was involved in a wide variety of cellular processes. Here, to investigate the distribution of ezrin, tissue microarray technology was employed to perform immunohistochemical experiments on human embryos, fetuses at 4 to 22 weeks' gestation, and adult tissue specimens. Results showed that ezrin was widely expressed in the gastrointestinal tract throughout the human developmental stages studied. At 6 to 8 weeks' gestation, ezrin was found in epithelial cells, and this staining pattern was particularly pronounced in the brush border of mature absorptive cells lining the villus in later developmental stages and adult tissues. Throughout neural development, ezrin was only expressed in the neural tube at 4 weeks' gestation. Ezrin was also detected in the cortex and medulla of the adrenal gland at 8 to 12 weeks' gestation, whereas its immunoreactivity was increased from the zona glomerulosa through the zona reticularis and was essentially undetectable in the adrenal medulla of adult tissues. Significant expression of ezrin was seen throughout development in the kidney, spleen, lymph nodes, and cells of stratified squamous epithelia. However, ezrin was undetectable in lung, liver, heart, and blood vessels. These results demonstrated that the expression pattern of ezrin was highly time specific and tissue specific.

Overexpression of neutrophil gelatinase-associated lipocalin and its receptor in colorectal carcinoma: Significant correlation with cell differentiation and tumour invasion.

Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin family, is related to imflammation and tumour. Recently, a specific cell-surface receptor (24p3R/NGALR) for lipocalin 24p3 was reported. However, the characteristics of NGALR expression in colorectal carcinoma (CRC) are not known. The objectives of this study were to investigate the expression of NGAL and NGALR in CRC specimens, and determine any relationship between the expression of these proteins and tumour progression. In the present study, CRC specimens of 102 patients were obtained, and the expression of NGAL, NGALR, ferritin and Ki67 was analyzed in paraffin sections by immunohistochemistry. Statistical analyses of the data collected were performed with SPSS software. We found that the cytoplasmic staining of NGAL, NGALR and ferritin, as well as the nuclear staining of Ki67 were significantly up-regulated in CRC tissues compared with normal colorectal tissues. Expression of NGAL was related to the deeper invasion of CRC (P=0.026), while NGALR was significantly associated with a deeper invasion (P=0.018) and a high degree of Tumor, Node and Metastasis stages (P=0.042) in CRC. The NGAL/NGALR co-expression was associated with poor cellular differentiation (P=0.004). Positive correlations between NGAL and NGALR (r=0.432, P<0.01), NGAL and ferritin (r=0.374, P<0.001), NGALR and Ki67 (r=0.228, P<0.05), NGAL/NGALR co-expression and ferritin (r=0.349, P<0.001), as well as NGAL/NGALR co-expression and Ki67 (r=0.205, P<0.05) were observed. However, the expression of NGAL or NGALR was not significantly associated with patient survival. These findings detected an elevated expression of NGAL and NGALR resulting in poor cellular differentiation and a deeper invasion of CRC. Thus, NGALR may be a novel target for the treatment of CRC.