Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era |
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| Authors: | Ritsuko Seki Koichi Ohshima Tomoaki Fujisaki Naokuni Uike Fumio Kawano Hisashi Gondo Shigeyoshi Makino Tetsuya Eto Yukiyoshi Moriuchi Fumihiro Taguchi Tomohiko Kamimura Hiroyuki Tsuda Ryosuke Ogawa Kazuya Shimoda Kiyoshi Yamashita Keiko Suzuki Hitoshi Suzushima Kunihiro Tsukazaki Masakazu Higuchi Atae Utsunomiya Masahiro Iwahashi Yutaka Imamura Kazuo Tamura Junji Suzumiya Minoru Yoshida Yasunobu Abe Tadashi Matsumoto Takashi Okamura |
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| Affiliation: | 1. Division of Hematology, Department of Medicine, Kurume University School of Medicine, Kurume;2. Research Center for Innovative Cancer Therapy, Kurume University, Kurume;3. Department of Pathology, Kurume University School of Medicine, Kurume;4. Department of Internal Medicine, Matsuyama Red Cross Hospital, Matsuyama;5. Department of Hematology, National Kyushu Cancer Center, Fukuoka;6. Department of Internal Medicine, National Hospital Organization Kumamoto Medical Center, Kumamoto;7. Department of Internal Medicine, Saga Prefectural Hospital, Koseikan, Saga;8. Department of Internal Medicine, Miyazaki Prefectural Hospital, Miyazaki;9. Department of Hematology, Hamanomachi Hospital, Fukuoka;10. Department of Hematology, Sasebo City General Hospital, Sasebo;11. Department of Hematology, Iizuka Hospital, Iizuka;12. Department of Hematology, Harasanshin General Hospital, Fukuoka;13. Division of Clinical Hematology, Kumamoto City Hospital, Kumamoto;14. Shimonoseki City Central Hospital, Shimonoseki;15. Department of Internal Medicine, Gastroenterology and Hematology, Faculty of Medicine, Miyazaki University, Kiyotake;16. Department of Internal Medicine, Koga General Hospital, Miyazaki;17. Department of Internal Medicine, NTT Nishinippon Kyushu General Hospital, Kumamoto;18. Molecular Medicine Unit and Hematology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki;19. Department of Internal Medicine, Kyushu Kosei‐nenkin Hospital, Kitakyushu;20. Department of Hematology, Imamura Bun‐in Hospital, Kagoshima;21. Department of Internal Medicine, Saiseikai‐Hita Hospital, Hita;22. Department of Hematology, St Mary Hospital, Kurume;23. Division of Medical Oncology and Hematology, Department of Medicine, Fukuoka University Hospital;24. Department of Internal Medicine, Fukuoka University Chikushi Hospital, Fukuoka;25. Japanese Red Cross Kumamoto Health Care Center, Kumamoto;26. Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka;27. Department of Hematology, Imamura Hon‐in Hospital, Kagoshima, Japan |
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| Abstract: | We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) ± rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 ( P = 0.022) or Bcl-6 ( P = 0.021), or GCB subtype ( P = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 ( P = 0.001) or MUM1 ( P = 0.011), or non-GCB subtype ( P = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group ( P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group ( P < 0.001) and also in the R-CHOP group ( P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated. ( Cancer Sci 2009; 100: 1842–1847) |
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