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The Characteristics of Epstein-Barr Virus (EBV)-positive Diffuse Large B-Cell Lymphoma: Comparison between EBV+ and EBV- Cases in Japanese Population

  1. Tetuo Kuze1,2,*,
  2. Naoya Nakamura1,
  3. Yuko Hashimoto1,
  4. Yoshikazu Sasaki1,
  5. Masafumi Abe1

Article first published online: 22 AUG 2005

DOI: 10.1111/j.1349-7006.2000.tb00909.x

Issue

Cancer Science

Cancer Science

Volume 91, Issue 12, pages 1233–1240, December 2000

Additional Information

How to Cite

Kuze, T., Nakamura, N., Hashimoto, Y., Sasaki, Y. and Abe, M. (2000), The Characteristics of Epstein-Barr Virus (EBV)-positive Diffuse Large B-Cell Lymphoma: Comparison between EBV+ and EBV- Cases in Japanese Population. Cancer Science, 91: 1233–1240. doi: 10.1111/j.1349-7006.2000.tb00909.x

Author Information

  1. 1

    First Department of Pathology, Fukushima Medical University, 1 Hikari-ga-oka, Fukushima 960–1295 and

  2. 2

    Safety Research Section, Research Department, TOAEIYO Ltd., 1 Tanaka, Iizaka, Fukushima 960–0280

* To whom correspondence should be addressed. E-mail: kuze.tetsuo@toaeiyo.ne.jp

Publication History

  1. Issue published online: 22 AUG 2005
  2. Article first published online: 22 AUG 2005
  3. (Received June 26, 2000/Revised September 19, 2000/Accepted September 25, 2000)

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Keywords:

  • Epstein-Barr virus;
  • Diffuse large B-cell lymphoma;
  • Immunoglobulin heavy chain genes;
  • Somatic mutation

We have investigated 114 cases with diffuse large B-cell lymphoma (DLBCL) to clarify the characteristics of DLBCL with Epstein-Barr virus (EBV) infection. Thirteen cases (11.4%) showed EBVencoded RNA 1 (EBER1) signals by RNA in situ hybridization. EBV-encoded latent membrane protein 1 (LMP1) and EBV-encoded nuclear antigen 2 (EBNA2) were expressed in 11 and 4 cases, respectively. Expression of CD30, Bcl-6 and immunoglobulin (Ig) was found in 92%, 31% and 23% with EBV+ DLBCL, and in 15%, 79% and 82% with EBV- DLBCL, respectively. The sequence of rearranged Ig heavy chain (IgH) variable (V) region gene was analyzed in 5 cases with EBV+ DLBCL and 61 cases with EBV- DLBCL. Somatic mutation was found in all cases except one with EBV- DLBCL. Average mutation frequency was 9.6% in EBV+ DLBCL vs. 11.5% in EBV- DLBCL. The rates of replacement mutation vs. silent mutation (R/S values) in complementarity determining region II and framework region III were 2.7 and 1.5 in EBV+ DLBCL, 2.6 and 1.4 in EBV- DLBCL. Crippling mutation generating a stop codon was found in 2 of 5 cases (40%) with EBV+ DLBCL, but none of 61 cases (0%) with EBV- DLBCL. These findings suggest that EBV+ DLBCL and EBV- DLBCL were both derived from germinal center (GC) or post-GCB cells, and EBV+ DLBCL frequently have a non-functional IgH gene owing to crippling mutation.

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