Ezrin expression and its phosphorylation in gastric carcinoma with lymphoid stroma and Epstein‑Barr virus infection

Tobo,Taro; Hirahashi,Minako; Yao,Takashi; Aishima,Shinichi; Oda,Yoshinao

doi:10.3892/mco.2012.56

Ezrin expression and its phosphorylation in gastric carcinoma with lymphoid stroma and Epstein‑Barr virus infection

Authors:
- Taro Tobo
- Minako Hirahashi
- Takashi Yao
- Shinichi Aishima
- Yoshinao Oda
View Affiliations

Affiliations: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
Published online on: December 28, 2012 https://doi.org/10.3892/mco.2012.56
Pages: 220-224

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gastric carcinoma with lymphoid stroma (GCLS) is a unique variant of gastric carcinoma that represents prominent lymphocytic infiltration and is correlated with Epstein‑Barr virus (EBV) infection. Ezrin expression and activation are crucial in tumor metastasis and induce cell migration of EBV‑related nasopharyngeal carcinomas. Using immunohistochemical methods, the expression of total and phosphorylated ezrin (p‑ezrin), Thr567, was examined in 104 GCLS cases, including 78 EBV‑positive and 26 EBV‑negative cases, as well as 29 non‑GCLS cases. Positive ezrin expression was detected to be at markedly higher levels in GCLS compared to non‑GCLS (P<0.0001). Furthermore, ezrin expression was detected to be at higher levels in EBV‑positive compared to EBV‑negative GCLS (P=0.0294). High expression of p‑ezrin in GCLS was associated with positive lymph node metastasis (P=0.0187). In summary, these results demonstrated that ezrin overexpression is correlated with the histologic characteristics of GCLS and EBV infection. Phosphorylation of ezrin may, therefore, contribute to lymph node metastasis in GCLS.

View Figures

View References

1	Watanabe H, Enjoji M and Imai T: Gastric carcinoma with lymphoid stroma. Its morphologic characteristics and prognostic correlations. Cancer. 38:232–243. 1976. View Article : Google Scholar : PubMed/NCBI
2	Weiss LM, Movahed LA, Butler AE, et al: Analysis of lymphoepithelioma and lymphoepithelioma-like carcinomas for Epstein-Barr viral genomes by in situ hybridization. Am J Surg Pathol. 13:625–631. 1989. View Article : Google Scholar : PubMed/NCBI
3	Nakamura S, Ueki T, Yao T, et al: Epstein-Barr virus in gastric carcinoma with lymphoid stroma. Special reference to its detection by the polymerase chain reaction and in situ hybridization in 99 tumors, including a morphologic analysis. Cancer. 73:2239–2249. 1994. View Article : Google Scholar
4	Matsunou H, Konishi F, Hori H, et al: Characteristics of Epstein-Barr virus-associated gastric carcinoma with lymphoid stroma in Japan. Cancer. 77:1998–2004. 1996. View Article : Google Scholar : PubMed/NCBI
5	Oda K, Tamaru J, Takenouchi T, et al: Association of Epstein-Barr virus with gastric carcinoma with lymphoid stroma. Am J Pathol. 143:1063–1071. 1993.PubMed/NCBI
6	Burke AP, Yen TS, Shekitka KM, et al: Lymphoepithelial carcinoma of the stomach with Epstein-Barr virus demonstrated by polymerase chain reaction. Mod Pathol. 3:377–380. 1990.PubMed/NCBI
7	Vaheri A, Carpén O, Heiska L, et al: The ezrin protein family: membrane-cytoskeleton interactions and disease associations. Curr Opin Cell Biol. 9:659–666. 1997. View Article : Google Scholar : PubMed/NCBI
8	Akisawa N, Nishimori I, Iwamura T, et al: High levels of ezrin expressed by human pancreatic adenocarcinoma cell lines with high metastatic potential. Biochem Biophys Res Commun. 258:395–400. 1999. View Article : Google Scholar : PubMed/NCBI
9	Sarrió D, Rodríguez-Pinilla SM, Dotor A, et al: Abnormal ezrin localization is associated with clinicopathological features in invasive breast carcinomas. Breast Cancer Res Treat. 98:71–79. 2006.PubMed/NCBI
10	Khanna C, Wan X and Bose S: The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 10:182–186. 2004. View Article : Google Scholar : PubMed/NCBI
11	Bal N, Yildirim S, Nursal TZ, et al: Association of ezrin expression in intestinal and diffuse gastric carcinoma with clinicopathological parameters and tumor type. World J Gastroenterol. 13:3726–3729. 2007.PubMed/NCBI
12	Zhao J, Zhang X and Xin Y: Up-regulated expression of Ezrin and c-Met proteins are related to the metastasis and prognosis of gastric carcinomas. Histol Histopathol. 26:1111–1120. 2011.PubMed/NCBI
13	Li L, Wang YY, Zhao ZS and Ma J: Ezrin is associated with gastric cancer progression and prognosis. Pathol Oncol Res. 17:909–915. 2011. View Article : Google Scholar : PubMed/NCBI
14	Endo K, Kondo S, Shackleford J, et al: Phosphorylated ezrin is associated with EBV latent membrane protein 1 in nasopharyngeal carcinoma and induces cell migration. Oncogene. 28:1725–1735. 2009. View Article : Google Scholar : PubMed/NCBI
15	Yamamoto H, Kohashi K, Oda Y, et al: Absence of human herpesvirus-8 and Epstein-Barr virus in inflammatory myofibroblastic tumor with anaplastic large cell lymphoma kinase fusion gene. Pathol Int. 56:584–590. 2006. View Article : Google Scholar : PubMed/NCBI
16	Fukayama M: Epstein-Barr virus and gastric carcinoma. Pathol Int. 60:337–350. 2010. View Article : Google Scholar : PubMed/NCBI
17	van Beek J, zur Hausen A, Klein Kranenbarg E, et al: EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement. J Clin Oncol. 22:664–670. 2004.PubMed/NCBI
18	Hino R, Uozaki H, Murakami N, et al: Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res. 69:2766–2774. 2009. View Article : Google Scholar : PubMed/NCBI
19	Elzagheid A, Korkeila E and Bendardaf R: Intense cytoplasmic ezrin immunoreactivity predicts poor survival in colorectal cancer. Hum Pathol. 39:1737–1743. 2008. View Article : Google Scholar : PubMed/NCBI
20	Kang YK, Hong SW, Lee H, et al: Prognostic implications of ezrin expression in human hepatocellular carcinoma. Mol Carcinog. 49:798–804. 2010.PubMed/NCBI
21	Moilanen J, Lassus H, Leminen A, et al: Ezrin immunoreactivity in relation to survival in serous ovarian carcinoma patients. Gynecol Oncol. 90:273–281. 2003. View Article : Google Scholar : PubMed/NCBI
22	Okamura D, Ohtsuka M, Kimura F, et al: Ezrin expression is associated with hepatocellular carcinoma possibly derived from progenitor cells and early recurrence after surgical resection. Mod Pathol. 21:847–855. 2008. View Article : Google Scholar
23	Kocher HM, Sandle J, Mirza TA, et al: Ezrin interacts with cortactin to form podosomal rosettes in pancreatic cancer cells. Gut. 58:271–284. 2009. View Article : Google Scholar : PubMed/NCBI
24	Pang J, Liu WP, Liu XP, et al: Profiling protein markers associated with lymph node metastasis in prostate cancer by DIGE-based proteomics analysis. J Proteome Res. 9:216–226. 2010. View Article : Google Scholar : PubMed/NCBI
25	Wang L, Lin GN, Jiang XL, et al: Expression of ezrin correlates with poor prognosis of nasopharyngeal carcinoma. Tumour Biol. 32:707–712. 2011. View Article : Google Scholar : PubMed/NCBI
26	Di Cristofano C, Leopizzi M, Miraglia A, et al: Phosphorylated ezrin is located in the nucleus of the osteosarcoma cell. Mod Pathol. 23:1012–1020. 2010.PubMed/NCBI
27	Tang F, Wang D, Duan C, et al: Berberine inhibits metastasis of nasopharyngeal carcinoma 5-8F cells by targeting Rho kinase-mediated Ezrin phosphorylation at threonine 567. J Biol Chem. 284:27456–27466. 2009. View Article : Google Scholar : PubMed/NCBI
28	Zhu L, Zhou R, Mettler S, et al: High turnover of ezrin T567 phosphorylation: conformation, activity, and cellular function. Am J Physiol Cell Physiol. 293:C874–C884. 2007. View Article : Google Scholar : PubMed/NCBI
29	Tran Quang C, Gautreau A, Arpin M, et al: Ezrin function is required for ROCK-mediated fibroblast transformation by the Net and Dbl oncogenes. EMBO J. 19:4565–4576. 2000.PubMed/NCBI
30	Cui Y, Li T, Zhang D and Han J: Expression of Ezrin and phosphorylated Ezrin (pEzrin) in pancreatic ductal adenocarcinoma. Cancer Invest. 28:242–247. 2010. View Article : Google Scholar : PubMed/NCBI
31	Wang HJ, Zhu JS, Zhang Q, et al: RNAi-mediated silencing of ezrin gene reverses malignant behavior of human gastric cancer cell line SGC-7901. J Dig Dis. 10:258–264. 2009. View Article : Google Scholar : PubMed/NCBI