Ezrin overexpression predicts the poor prognosis of gastric adenocarcinoma
Ezrin is a cytoskeletal protein that is involved in tumor growth and invasion. It has been suggested that Ezrin expression plays an important role in tumor metastasis. This study is aimed to investigate the clinicopathological significance of Ezrin overexpression in gastric adenocarcinomas.
Ezrin protein expression was examined by immunohistochemistry in 26 normal gastric mucosa, 32 dysplasia, and 277 gastric adenocarcinomas. The relationship between Ezrin expression and the clinicopathological features of gastric cancers was analyzed. In addition, a gastric cancer cell line, MKN-1, was also used for immunofluorescence staining to evaluate the distribution of Ezrin protein.
Ezrin protein located in the cytoplasm and/or membrane in the migrating gastric cancer cells, and it mainly concentrated at the protrusion site; however, only cytoplasmic distribution was observed in the non-migrating cancer cells by immunofluorescence staining. The positive rate of Ezrin protein expression was significantly higher in gastric adenocarcinoma and dysplasia compared with that in the normal gastric mucosa. Moreover, expression frequency of Ezrin protein increased significantly in lymph node metastasis and late clinical stages. Consistently, strong expression of Ezrin was significantly correlated with poor prognosis of gastric cancer.
The detection of Ezrin expression can be used as the marker for early diagnosis and prognosis of gastric adenocarcinoma.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2303598677653946
- Youn HG, An JY, Choi MG, Noh JH, Sohn TS, Kim S: Recurrence after curative resection of early gastric cancer. Ann Surg Oncol 2010, 17:448–454. CrossRef
- Fan LL, Chen DF, Lan CH, Liu KY, Fang DC: Knockdown of ezrin via RNA interference suppresses Helicobacter pylori-enhanced invasion of gastric cancer cells. Cancer Biol Ther 2011, 11:746–752. CrossRef
- Elzagheid A, Algars A, Bendardaf R, Lamlum H, Ristamaki R, Collan Y, Syrjanen K, Pyrhonen S: E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome. World J Gastroenterol 2006, 12:4304–4309.
- McClatchey AI: Merlin and ERM proteins: unappreciated roles in cancer development. Nat Rev Cancer 2003, 3:877–883. CrossRef
- Hunter KW: Ezrin, a key component in tumor metastasis. Trends Mol Med 2004, 10:201–204. CrossRef
- Louvet-Vallee S: ERM proteins:from cellular architecture to cell signaling. Biol Cell 2000, 92:305–316. CrossRef
- Yu Y, Khan J, Khanna C, Helman L, Meltzer PS, Merlino G: Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic egulators. Nat Med 2004, 10:175–181. CrossRef
- Mak H, Naba A, Varma S, Schick C, Day A, Sengupta SK, Arpin M, Elliott BE: Ezrin phosphorylation on tyrosine 477 regulates invasion and metastasis of breast cancer cells. BMC Cancer 2012, 12:82. CrossRef
- Gould KL, Bretscher A, Esch FS, Hunter T: cDNA cloning and sequencing of the protein-tyrosine kinase substrate, ezrin, reveals homology to band 4.1. EMBO J 1989, 8:4133–4142.
- Bretscher A, Edwards K, Fehon RG: ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol 2002, 3:586–599. CrossRef
- Wu B, Li J, Huang D, Wang W, Chen Y, Liao Y, Tang X, Xie H, Tang F: Baicalein mediates inhibition of migration and invasiveness of skin carcinoma through Ezrin in A431 cells. BMC Cancer 2011, 11:527. CrossRef
- Mäkitie T, Carpén O, Vaheri A, Kivelä T: Ezrin as a prognostic indicator and its relationship to tumor characteristics in uveal malignant melanoma. Invest Ophthalmol Vis Sci 2001, 42:2442–2449.
- Weng WH, Ahlén J, Aström K, Lui WO, Larsson C: Prognostic impact of immunohistochemical expression of ezrin in highly malignant soft tissue sarcomas. Clin Cancer Res 2005, 11:6198–6204. CrossRef
- Meng Y, Lu Z, Yu S, Zhang Q, Ma Y, Chen J: Ezrin promotes invasion and metastasis of pancreatic cancer cells. J Transl Med 2010, 8:61. CrossRef
- Chen Y, Wang D, Guo Z, Zhao J, Wu B, Deng H, Zhou T, Xiang H, Gao F, Yu X, Liao J, Ward T, Xia P, Emenari C, Ding X, Thompson W, Ma K, Zhu J, Aikhionbare F, Dou K, Cheng SY, Yao X: Rho Kinase Phosphorylation Promotes Ezrin-Mediated Metastasis in Hepatocellular Carcinoma. Cancer Res 2011, 71:1721–1729. CrossRef
- Zheng S, Huang J, Zhou K, Zhang C, Xiang Q, Tan Z, Wang T, Fu X: 17-Estradiol enhances breast cancer cell motility and invasion via extra-nuclear activation of actin-binding protein Ezrin. PLoS One 2011, 6:e22439. CrossRef
- Zhu J, Feng Y, Ke Z, Yang Z, Zhou J, Huang X, Wang L: Down-Regulation of miR-183 Promotes Migration and Invasion of Osteosarcoma by Targeting Ezrin. Am J Pathol 2012,180(6):2440–2451. CrossRef
- Bal N, Yildirim S, Nursal TZ, Bolat F, Kayaselcuk F: Association of ezrin expression in intestinal and diffuse gastric carcinoma with clinicopathological parameters and tumor type. World J Gastroenterol 2007, 13:3726–3729.
- Zhao J, Zhang X, Xin Y: Up-regulated expression of Ezrin and c-Met proteins are related to the metastasis and prognosis of gastric carcinomas. Histol Histopathol 2011, 26:1111–1120.
- Li L, Wang YY, Zhao ZS, Ma J: Ezrin is associated with gastric cancer progression and prognosis. Pathol Oncol Res 2011, 17:909–915. CrossRef
- AJCC: AJCC Cancer Staging Manual. 6th edition. New York: Springer Verlag; 2002.
- Elzagheid A, Korkeila E, Bendardaf R, Buhmeida A, Heikkilä S, Vaheri A, Syrjänen K, Pyrhönen S, Carpén O: Intense cytoplasmic ezrin immunoreactivity predicts poor survival in colorectal cancer. Hum Pathol 2008, 39:1737–1743. CrossRef
- Demirag GG, Sullu Y, Gurgenyatagi D, Okummus NO, Yucel I: Expression of Plakophilins (PKP1, PKP22, and PKP3) in gastric cancers. Diagn Pathol 2011, 6:1–5. CrossRef
- Brenner H, Rothenbacher D, Arndt : Epidemiology of stomach cancer. Methods Mol Biol 2009, 472:467–477. CrossRef
- Fais S: A role for ezrin in a neglected metastatic tumor function. Trends Mol Med 2004, 10:249–250. CrossRef
- Wang HJ, Zhu JS, Zhang Q, Guo H, Dai YH, Xiong XP: RNAi-mediated silencing of ezrin gene reverses malignant behavior of human gastric cancer cell line SGC-7901. J Dig Dis 2009, 10:258–264. CrossRef
- Briggs JW, Ren L, Nguyen R, Chakrabarti , Cassavaugh J, Rahim S, Bulut G, Zhou M, Veenstra TD, Chen Q, Wei JS, Khan J, Uren A, Khanna C: The ezrin metastatic phenotype is associated with the initiation of protein translation. Neoplasia 2012, 14:297–310.
- Berryman M, Franck Z, Kawai A: Ezrin is concentrated in the apical microvilli of a wide variety of epithelial cells whereas moesin is found primarily in endothelial cells. J Cell Sci 1993, 105:1025–1043.
- Köbel M, Langhammer T, Hüttelmaier S, Schmitt WD, Kriese K, Dittmer J, Strauss HG, Thomssen C, Hauptmann S: Ezrin expression is related to poor prognosis in FIGO stage I endometrioid carcinomas. Mod Pathol 2006, 19:581–587. CrossRef
- Yasuoka H, Tsujimoto M, Inagaki M, Kodama R, Tsuji H, Iwahashi Y, Mabuchi Y, Ino K, Sanke T, Nakamura Y: Clinicopathological significance of podocalyxin and phosphorylated ezrin in uterine endometrioid adenocarcinoma. J Clin Pathol 2012,65(5):399–402. CrossRef
- Catalano V, Labianca R, Beretta GD, Gatta G, de Braoud F, Van Cusem E: Gastric cancer. Crit Rev Oncol Hematol. 2009,71(2):127–164. CrossRef
- Lam EK, Wang X, Shin VY, Zhang S, Morrison H, Sun J, Ng EK, Yu J, Jin H: A microRNA contribution to aberrant Ras activation in gastric cancer. Am J Transl Res 2011, 3:209–218.
- Ezrin overexpression predicts the poor prognosis of gastric adenocarcinoma
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
- Online Date
- October 2012
- Online ISSN
- BioMed Central
- Additional Links
- Gastric adenocarcinoma
- Tissue microarray
- Author Affiliations
- 1. Department of Pathology, Yanbian University Medical College, Yanji-City, 133002, Jilin-Prov., P.R. China
- 4. Department of Internal Medicine, Yanbian University Affiliated Hospital, Yanji-City, 133000, Jilin-Prov., P.R. China
- 2. Cancer Research Center, Yanbian University, Yanji-City, 133002, Jilin-Prov., P.R. China
- 3. Department of Pathophysiology, Yanbian University Medical College, Yanji-City, 133002, Jilin-Prov., P.R. China