Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas

BACKGROUND: Fascin is an actin bundling protein with roles in the formation of cell protrusions and motility of mesenchymal and neuronal cells. Fascin is normally low or absent from epithelia, but is upregulated in several epithelial neoplasms where it may contribute to an invasive phenotype. Here, we report on the prevalence and potential clinical significance of fascin expression in relation to the progression of colorectal adenocarcinoma and to tumor cell proliferation as measured by Ki67 index. METHODS: Conventional tissue sections of 107 colorectal adenomas and 35 adenocarcinomas were analyzed by immunohistochemistry for fascin and Ki67 expression. Fascin expression and Ki67 proliferation index were also investigated by use of a tissue microarray containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas linked to a CCF, IRB-approved database with a mean of 38 months of clinical follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox regression methods. RESULTS: Fascin was not expressed by the normal colonic epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas showed fascin expression in greater than 10% of the tumor cells. In the clinically-annotated tumors, fascin immunoreactivity was more common in tumors located in the proximal colon (p = 0.009), but was not associated with age, gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62) with strong fascin immunoreactivity had a worse prognosis than patients with low or absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative patients; p = 0.023). In adenomas, fascin and Ki67 tended to be inversely correlated at the cellular level; this trend was less apparent in adenocarcinomas. CONCLUSION: Fascin is upregulated in a proportion of adenomas, where its expression is often focal. Strong and diffuse expression was seen in a subset of advanced colorectal adenocarcinomas that correlated with shorter survival in stage III and IV patients. Fascin may have prognostic value as an early biomarker for more aggressive colorectal adenocarcinomas

Microarray gene expression profiling and analysis in renal cell carcinoma

BACKGROUND: Renal cell carcinoma (RCC) is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. METHODS: Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. RESULTS: Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR). Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. CONCLUSIONS: This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most notably, genes involved in cell adhesion were dominantly up-regulated whereas genes involved in transport were dominantly down-regulated. This study reveals significant gene expression alterations in key biological pathways and provides potential insights into understanding the molecular mechanism of renal cell carcinogenesis

Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas:an immunohistochemical study of clinically annotated tumors

Syndecan-1 is a transmembrane proteoglycan with important roles in cell-cell and cell-extracellular matrix adhesion and as a growth factor co-receptor. Syndecan-1 is highly expressed by normal epithelial cells and loss of expression has been associated with epithelial-mesenchymal transition and the transformed phenotype. Loss of epithelial syndecan-1 has been reported in human colorectal adenocarcinomas, but whether this has prognostic significance remains undecided. Here we have examined syndecan-1 expression and its potential prognostic value with reference to a clinically annotated tissue microarray for human colon adenocarcinomas

Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: An immunohistochemical study of clinically annotated tumors-2

Us. d, example of a moderately differentiated adenocarcinoma with strong stromal staining for syndecan-1 and moderate staining of the tumor. e, f, contiguous sections of the same tumor stained for syndecan-1, (e), or fascin, (f), demonstrating strong staining for fascin in the stroma (arrowed). The tumor cells are negative for fascin and syndecan-1. Isolated strongly fascin positive cells correspond to dendritic and vascular endothelial cells and provideinternal positive controls for the fascin staining.<p><b>Copyright information:</b></p><p>Taken from "Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: An immunohistochemical study of clinically annotated tumors"</p><p>http://www.biomedcentral.com/1471-2407/8/185</p><p>BMC Cancer 2008;8():185-185.</p><p>Published online 30 Jun 2008</p><p>PMCID:PMC2459187.</p><p></p

Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: An immunohistochemical study of clinically annotated tumors-0

Us. d, example of a moderately differentiated adenocarcinoma with strong stromal staining for syndecan-1 and moderate staining of the tumor. e, f, contiguous sections of the same tumor stained for syndecan-1, (e), or fascin, (f), demonstrating strong staining for fascin in the stroma (arrowed). The tumor cells are negative for fascin and syndecan-1. Isolated strongly fascin positive cells correspond to dendritic and vascular endothelial cells and provideinternal positive controls for the fascin staining.<p><b>Copyright information:</b></p><p>Taken from "Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: An immunohistochemical study of clinically annotated tumors"</p><p>http://www.biomedcentral.com/1471-2407/8/185</p><p>BMC Cancer 2008;8():185-185.</p><p>Published online 30 Jun 2008</p><p>PMCID:PMC2459187.</p><p></p