Mantle cell lymphoma shows three morphological evolutions of classical, intermediate, and aggressive forms, which occur in parallel with increased labeling index of cyclin D1 and Ki-67

Yoshizo Kimura, Kensaku Sato, Fumiko Arakawa, Kennosuke Karube, Yuko Nomura, Kei Shimizu, Ryosuke Aoki, Keiko Hashikawa, Shiro Yoshida, Junichi Kiyasu, Masanori Takeuchi, Daisuke Nino, Yasuo Sugita, Toshiaki Morito, Tadashi Yoshino, Shigeo Nakamura, Masahiro Kikuchi, Koichi Ohshima

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Abstract

Although the 2008 World Health Organization classification defines two subtypes of mantle cell lymphoma (MCL), classical and aggressive, we often encounter MCL with both features in the same site. We named this feature "MCL with focal aggressive form (intermediate MCL)" In the present study, we reclassified 237 patients with cyclin D1 (CCND1)-positive MCL on the basis of the concept of intermediate MCL, and analyzed the correlation of this reclassification with immunohistochemical detection of CCND1, Ki-67, p53, p27Kip1, and p21WAF/Cip1. The median overall survival was 77, 31, and 18 months for classical, intermediate, and aggressive MCL, respectively, showing a statistically significant difference (P <0.0001). The expression levels of CCND1, Ki-67, p53, and p21WAF/Cip1 in aggressive MCL (mean 80.1 ± 27.8%, 73.7 ± 28.9%, 31.0 ± 69.0%, and 10.4 ± 24.8%, respectively) were higher than those in classical MCL (mean 58.1 ± 36.7%, 25.2 ± 25.5%, 6.5 ± 24.3%, and 2.5 ± 13.0%, respectively) and intermediate MCL (mean 75.7 ± 31.4%, 30.8 ± 33.3%, 21.0 ± 57.4%, and 4.8 ± 16.5%, respectively). Significantly different levels of Ki-67 and p21WAF/Cip1 were only recognized between intermediate and aggressive (P <0.05 and P <0.0001, respectively), whereas those of CCND1 and p53 were only between classical and intermediate (P <0.0001 and P <0.05, respectively). There were no significant differences in p27Kip1 among the three groups. The subsequent discriminant analysis with independent prognostic factors clearly demonstrated that the morphological evolution of MCL occurs in parallel with increased labeling index of CCND1 and Ki-67. The diagnosis of intermediate MCL thus proved to be of major significance and should enable the design of more tailored therapies.

Original languageEnglish
Pages (from-to)806-814
Number of pages9
JournalCancer Science
Volume101
Issue number3
DOIs
Publication statusPublished - Mar 2010

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Mantle-Cell Lymphoma
Cyclin D1
Discriminant Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Mantle cell lymphoma shows three morphological evolutions of classical, intermediate, and aggressive forms, which occur in parallel with increased labeling index of cyclin D1 and Ki-67. / Kimura, Yoshizo; Sato, Kensaku; Arakawa, Fumiko; Karube, Kennosuke; Nomura, Yuko; Shimizu, Kei; Aoki, Ryosuke; Hashikawa, Keiko; Yoshida, Shiro; Kiyasu, Junichi; Takeuchi, Masanori; Nino, Daisuke; Sugita, Yasuo; Morito, Toshiaki; Yoshino, Tadashi; Nakamura, Shigeo; Kikuchi, Masahiro; Ohshima, Koichi.

In: Cancer Science, Vol. 101, No. 3, 03.2010, p. 806-814.

Research output: Contribution to journalArticle

Kimura, Y, Sato, K, Arakawa, F, Karube, K, Nomura, Y, Shimizu, K, Aoki, R, Hashikawa, K, Yoshida, S, Kiyasu, J, Takeuchi, M, Nino, D, Sugita, Y, Morito, T, Yoshino, T, Nakamura, S, Kikuchi, M & Ohshima, K 2010, 'Mantle cell lymphoma shows three morphological evolutions of classical, intermediate, and aggressive forms, which occur in parallel with increased labeling index of cyclin D1 and Ki-67', Cancer Science, vol. 101, no. 3, pp. 806-814. https://doi.org/10.1111/j.1349-7006.2009.01433.x
Kimura, Yoshizo ; Sato, Kensaku ; Arakawa, Fumiko ; Karube, Kennosuke ; Nomura, Yuko ; Shimizu, Kei ; Aoki, Ryosuke ; Hashikawa, Keiko ; Yoshida, Shiro ; Kiyasu, Junichi ; Takeuchi, Masanori ; Nino, Daisuke ; Sugita, Yasuo ; Morito, Toshiaki ; Yoshino, Tadashi ; Nakamura, Shigeo ; Kikuchi, Masahiro ; Ohshima, Koichi. / Mantle cell lymphoma shows three morphological evolutions of classical, intermediate, and aggressive forms, which occur in parallel with increased labeling index of cyclin D1 and Ki-67. In: Cancer Science. 2010 ; Vol. 101, No. 3. pp. 806-814.
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abstract = "Although the 2008 World Health Organization classification defines two subtypes of mantle cell lymphoma (MCL), classical and aggressive, we often encounter MCL with both features in the same site. We named this feature {"}MCL with focal aggressive form (intermediate MCL){"} In the present study, we reclassified 237 patients with cyclin D1 (CCND1)-positive MCL on the basis of the concept of intermediate MCL, and analyzed the correlation of this reclassification with immunohistochemical detection of CCND1, Ki-67, p53, p27Kip1, and p21WAF/Cip1. The median overall survival was 77, 31, and 18 months for classical, intermediate, and aggressive MCL, respectively, showing a statistically significant difference (P <0.0001). The expression levels of CCND1, Ki-67, p53, and p21WAF/Cip1 in aggressive MCL (mean 80.1 ± 27.8{\%}, 73.7 ± 28.9{\%}, 31.0 ± 69.0{\%}, and 10.4 ± 24.8{\%}, respectively) were higher than those in classical MCL (mean 58.1 ± 36.7{\%}, 25.2 ± 25.5{\%}, 6.5 ± 24.3{\%}, and 2.5 ± 13.0{\%}, respectively) and intermediate MCL (mean 75.7 ± 31.4{\%}, 30.8 ± 33.3{\%}, 21.0 ± 57.4{\%}, and 4.8 ± 16.5{\%}, respectively). Significantly different levels of Ki-67 and p21WAF/Cip1 were only recognized between intermediate and aggressive (P <0.05 and P <0.0001, respectively), whereas those of CCND1 and p53 were only between classical and intermediate (P <0.0001 and P <0.05, respectively). There were no significant differences in p27Kip1 among the three groups. The subsequent discriminant analysis with independent prognostic factors clearly demonstrated that the morphological evolution of MCL occurs in parallel with increased labeling index of CCND1 and Ki-67. The diagnosis of intermediate MCL thus proved to be of major significance and should enable the design of more tailored therapies.",
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AU - Karube, Kennosuke

AU - Nomura, Yuko

AU - Shimizu, Kei

AU - Aoki, Ryosuke

AU - Hashikawa, Keiko

AU - Yoshida, Shiro

AU - Kiyasu, Junichi

AU - Takeuchi, Masanori

AU - Nino, Daisuke

AU - Sugita, Yasuo

AU - Morito, Toshiaki

AU - Yoshino, Tadashi

AU - Nakamura, Shigeo

AU - Kikuchi, Masahiro

AU - Ohshima, Koichi

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N2 - Although the 2008 World Health Organization classification defines two subtypes of mantle cell lymphoma (MCL), classical and aggressive, we often encounter MCL with both features in the same site. We named this feature "MCL with focal aggressive form (intermediate MCL)" In the present study, we reclassified 237 patients with cyclin D1 (CCND1)-positive MCL on the basis of the concept of intermediate MCL, and analyzed the correlation of this reclassification with immunohistochemical detection of CCND1, Ki-67, p53, p27Kip1, and p21WAF/Cip1. The median overall survival was 77, 31, and 18 months for classical, intermediate, and aggressive MCL, respectively, showing a statistically significant difference (P <0.0001). The expression levels of CCND1, Ki-67, p53, and p21WAF/Cip1 in aggressive MCL (mean 80.1 ± 27.8%, 73.7 ± 28.9%, 31.0 ± 69.0%, and 10.4 ± 24.8%, respectively) were higher than those in classical MCL (mean 58.1 ± 36.7%, 25.2 ± 25.5%, 6.5 ± 24.3%, and 2.5 ± 13.0%, respectively) and intermediate MCL (mean 75.7 ± 31.4%, 30.8 ± 33.3%, 21.0 ± 57.4%, and 4.8 ± 16.5%, respectively). Significantly different levels of Ki-67 and p21WAF/Cip1 were only recognized between intermediate and aggressive (P <0.05 and P <0.0001, respectively), whereas those of CCND1 and p53 were only between classical and intermediate (P <0.0001 and P <0.05, respectively). There were no significant differences in p27Kip1 among the three groups. The subsequent discriminant analysis with independent prognostic factors clearly demonstrated that the morphological evolution of MCL occurs in parallel with increased labeling index of CCND1 and Ki-67. The diagnosis of intermediate MCL thus proved to be of major significance and should enable the design of more tailored therapies.

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