J Korean Med Sci.  2007 Oct;22(5):855-861. 10.3346/jkms.2007.22.5.855.

Epstein-Barr Virus, Beta-Catenin, and E-cadherin in Gastric Carcinomas

• Jung IM
• Chung JK
• Kim YA
• Kim JE
• Heo SC
• Ahn YJ
• Hwang KT
• Kim BG
• Lee KL
• Kim CW
• Kim WH
• Chang MS

• KMID: 1713293
• DOI: http://doi.org/10.3346/jkms.2007.22.5.855

Abstract

Activated beta-catenin is suggested to inhibit NF-kappaB activation, and we previously demonstrated that NF-kappaB nuclear positivity was more frequent in Epstein-Barr virus (EBV)-infected gastric carcinomas. It is controversial that beta-catenin and E-cadherin are prognostic markers in gastric carcinomas. To define a relationship between beta-catenin and EBV, and the prognostic value of beta-catenin and E-cadherin, we analyzed in situ hybridization for EBV-encoded small RNAs, betacatenin, and E-cadherin immunohistochemistry, and clinicophatological features in 111 gastric carcinomas. EBV infection was detected in seven carcinomas (6.3%); none of seven showed beta-catenin nuclear accumulation, and five out of seven revealed beta-catenin membranous loss or cytoplamic expression. Eighty cases (72.1%) showed beta-catenin alteration; i.e., loss of membrane staining in 65 (58.6 %), cytoplasmic expression in 35 (31.5%), and nuclear accumulation in 15 (13.5%). E-cadherin alteration was observed in 34 cases (30.6%) and correlated with betacatenin alteration. On multivariate analysis, the combined immunoexpression group of beta-catenin nuclear accumulation/ E-cadherin alteration and the advanced TNM cancer stage group showed poor patient's survival (p<0.05). In conclusion, betacatenin activation through nuclear accumulation hardly occurred in EBV-infected gastric carcinomas. The combined immunoexpression pattern of beta-catenin and E-cadherin can be used as a prognostic marker in gastric carcinomas.

Keyword

Stomach Neoplasms; Herpesvirus 4, Human; Beta Catenin; Cadherins; Prognosis

MeSH Terms

Adult
Aged
Cadherins/*metabolism
Carcinoma/*metabolism/*virology
Cell Nucleus/metabolism
Female
*Gene Expression Regulation, Neoplastic
*Gene Expression Regulation, Viral
Herpesvirus 4, Human/*metabolism
Humans
Immunohistochemistry/methods
In Situ Hybridization
Male
Middle Aged
NF-kappa B/metabolism
Prognosis
Stomach Neoplasms/*metabolism/*virology
beta Catenin/*metabolism

Figure

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  Fig. 1 Representative features of in situ hybridization for Epstein-Barr virus (A) and immunohistochemistry for beta-catenin (B-D) and E-cadherin (E-F). (A) Most of cancer cell nuclei reveal strong signals of black or dark navy aggregates on in situ hybridization for Epstein-Barr virus, while normal stroma cell nuclei produce no signal (×200). (B) Beta-catenin shows loss of membranous staining in cancer cells (left 2/3), while preserved membranous staining in normal epithelium (right 1/3) (×100). (C) Beta-catenin reveals cytoplasmic expression without nuclear accumulation in cancer cells (×200). (D) Beta-catenin demonstrates nuclear accumulation in cancer cells without cytoplasmic expression (×400). (E) E-cadherin discloses loss of membranous staining in cancer cells (right 2/3), while preserved membranous staining in normal epithelium (left 1/3) (×200). (F) E-cadherin exhibits well preserved membranous staining in cancer cells (×200).

• 

  Fig. 2 Kaplan-Meier survival plots. Combined immunoexpression of beta-catenin nuclear pattern/E-cadherin (A), TNM tumor stage (B), and beta-catenin nuclear accumulation (C). (A) Group 4 (with a combined pattern of beta-catenin nuclear accumulation/E-cadherin alteration) shows a poor patient survival (p=0.001). Group 1, a group with a combined pattern of beta-catenin no nuclear accumulation/normal E-cadherin; Group 2, beta-catenin nuclear accumulation/normal E-cadherin; Group 3, beta-catenin no nuclear accumulation/E-cadherin alteration; and Group 4, beta-catenin nuclear accumulation/E-cadherin alteration. (B) Advanced TNM tumor stage group has a lower rate of patient survival (p=0.008). (C) Beta-catenin nuclear accumulation group has a marginal impact on the patient survival (p=0.077).

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