Immunohistochemical expression of Fascin-1 in colorectal cancer in relation to clinical and pathological parameters
Abstract
Introduction. Fascins are a group of proteins taking part in the maintenance of a proper structure of the cellular cytoskeleton. Fascin-1 is an actin-bundling protein present in neurons, fibroblasts, endothelial, smooth muscle, dendritic and mesenchymal cells whereas lack of its expression is characteristic of epithelial cells. Fascin-1 overexpression can be observed in neoplastic cells. Therefore, the aim of this study was to assess the expression of Fascin-1 protein in patients with colorectal cancer (CRC) and to analyze associations between Fascin-1 expression and clinical-pathological parameters. Material and methods. The study material included postoperative samples (tumor and unchanged colon tissue) obtained from 51 CRC patients. Fascin-1 expression was assessed in the paraffin sections by immunohistochemistry. Results. A statistically significant correlation was found between the histological type of cancer and the expression of Fascin-1 (p = 0.012). Increased expression of Fascin-1 in CRC was more frequent in adenocarcinoma type without the mucosal component with a better prognosis and decreased expression of this protein correlated with infiltration of cancer cells to blood and lymphatic vessels (p = 0.038). Conclusions. Our findings indicate a potential role of Fascin-1 in the pathogenesis of colon cancer; however, further studies will show whether this protein plays a role in the infiltration of colorectal cancer cells.
Keywords: colorectal cancerFascin-1metastasisIHC
References
- Torre LA, Siegel RL, Ward EM, et al. Global Cancer Incidence and Mortality Rates and Trends--An Update. Cancer Epidemiol Biomarkers Prev. 2016; 25(1): 16–27.
- Marley AR, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet. 2016; 7(3): 105–114.
- Fletcher DA, Mullins RD. Cell mechanics and the cytoskeleton. Nature. 2010; 463(7280): 485–492.
- Dominguez R, Holmes KC. Actin structure and function. Annu Rev Biophys. 2011; 40: 169–186.
- Stricker J, Falzone T, Gardel ML. Mechanics of the F-actin cytoskeleton. J Biomech. 2010; 43(1): 9–14.
- Hashimoto Y, Skacel M, Adams JC. Roles of fascin in human carcinoma motility and signaling: prospects for a novel biomarker? Int J Biochem Cell Biol. 2005; 37(9): 1787–1804.
- Adams JC. Roles of fascin in cell adhesion and motility. Curr Opin Cell Biol. 2004; 16(5): 590–596.
- Jayo A, Parsons M. Fascin: a key regulator of cytoskeletal dynamics. Int J Biochem Cell Biol. 2010; 42(10): 1614–1617.
- Kanda Y, Kawaguchi T, Kuramitsu Y, et al. Fascin regulates chronic inflammation-related human colon carcinogenesis by inhibiting cell anoikis. Proteomics. 2014; 14(9): 1031–1041.
- Kulasingam V, Diamandis EP. Fascin-1 is a novel biomarker of aggressiveness in some carcinomas. BMC Med. 2013; 11: 53.
- Jawhari AU, Buda A, Jenkins M, et al. Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro. Am J Pathol. 2003; 162(1): 69–80.
- Cheng M, Xue H, Cao W, et al. Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling. J Biol Chem. 2016; 291(24): 12871–12879.
- Li A, Dawson JC, Forero-Vargas M, et al. The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion. Curr Biol. 2010; 20(4): 339–345.
- Sobin LH, Gospodarowicz MK, Wittekind Ch. TNM classification of malignant tumours. Wiley-Blackwell. Oxford 2009.
- Guzińska-Ustymowicz K. Tumor budding in colorectal cancer: recent progress in colorectal cancer research. Tetsuichiro Muto E, Mochizuki H, Masaki T.New York: Nova Biomedical Books. Chapter: Aggressive and non-aggressive tumor budding in colorectal cancers. ; 2006: 105–116.
- Jass JR, Love SB, Northover JM. A new prognostic classification of rectal cancer. Lancet. 1987; 1(8545): 1303–1306.
- Ma Y, Machesky LM. Fascin1 in carcinomas: Its regulation and prognostic value. Int J Cancer. 2015; 137(11): 2534–2544.
- Tan VY, Lewis SJ, Adams JC, et al. Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: a systematic review and meta-analysis. BMC Med. 2013; 11: 52.
- Yamashiro S, Yamakita Y, Ono S, et al. Fascin, an actin-bundling protein, induces membrane protrusions and increases cell motility of epithelial cells. Mol Biol Cell. 1998; 9(5): 993–1006.
- Vignjevic D, Schoumacher M, Gavert N, et al. Fascin, a novel target of beta-catenin-TCF signaling, is expressed at the invasive front of human colon cancer. Cancer Res. 2007; 67(14): 6844–6853.
- Vignjevic D, Kojima Si, Aratyn Y, et al. Role of fascin in filopodial protrusion. J Cell Biol. 2006; 174(6): 863–875.
- Hashimoto Y, Parsons M, Adams JC. Dual actin-bundling and protein kinase C-binding activities of fascin regulate carcinoma cell migration downstream of Rac and contribute to metastasis. Mol Biol Cell. 2007; 18(11): 4591–4602.
- Schoumacher M, El-Marjou F, Laé M, et al. Conditional expression of fascin increases tumor progression in a mouse model of intestinal cancer. Eur J Cell Biol. 2014; 93(10-12): 388–395.
- Li A, Morton JP, Ma Y, et al. Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes. Gastroenterology. 2014; 146(5): 1386–13896.e1.
- Kim SuJ, Kim DC, Kim MC, et al. Fascin expression is related to poor survival in gastric cancer. Pathol Int. 2012; 62(12): 777–784.
- Yoder BJ, Tso E, Skacel M, et al. The expression of fascin, an actin-bundling motility protein, correlates with hormone receptor-negative breast cancer and a more aggressive clinical course. Clin Cancer Res. 2005; 11(1): 186–192.
- Lin Ck, Su HY, Tsai WC, et al. Association of cortactin, fascin-1 and epidermal growth factor receptor (EGFR) expression in ovarian carcinomas: correlation with clinicopathological parameters. Dis Markers. 2008; 25(1): 17–26.
- Lee TK, Poon RTP, Man K, et al. Fascin over-expression is associated with aggressiveness of oral squamous cell carcinoma. Cancer Lett. 2007; 254(2): 308–315.
- Puppa G, Maisonneuve P, Sonzogni A, et al. Independent prognostic value of fascin immunoreactivity in stage III-IV colonic adenocarcinoma. Br J Cancer. 2007; 96(7): 1118–1126.
- Hashimoto Y, Skacel M, Lavery IC, et al. Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas. BMC Cancer. 2006; 6: 241.
- Oh SY, Kim YB, Suh KW, et al. Prognostic impact of fascin-1 expression is more significant in advanced colorectal cancer. J Surg Res. 2012; 172(1): 102–108.
- Tsai WC, Chao YC, Sheu LF, et al. Overexpression of fascin-1 in advanced colorectal adenocarcinoma: tissue microarray analysis of immunostaining scores with clinicopathological parameters. Dis Markers. 2007; 23(3): 153–160.
- Ozerhan IH, Ersoz N, Onguru O, et al. Fascin expression in colorectal carcinomas. Clinics (Sao Paulo). 2010; 65(2): 157–164.
- Yamamoto H, Kohashi K, Fujita A, et al. Fascin-1 overexpression and miR-133b downregulation in the progression of gastrointestinal stromal tumor. Mod Pathol. 2013; 26(4): 563–571.