title: 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.
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, p27(Kip1), and p21(WAF/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 p21(WAF/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 p21(WAF/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 p27(Kip1) 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.
authors.affiliation: Department of Pathology, School of Medicine, Kurume University, Kurume, Japan. yoshizo830@yahoo.co.jp
authors.forename: Yoshizo
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kensaku
authors.initials: K
authors.lastname: Sato
authors.forename: Fumiko
authors.initials: F
authors.lastname: Arakawa
authors.forename: Kennosuke
authors.initials: K
authors.lastname: Karube
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nomura
authors.forename: Kei
authors.initials: K
authors.lastname: Shimizu
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Aoki
authors.forename: Keiko
authors.initials: K
authors.lastname: Hashikawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Yoshida
authors.forename: Junichi
authors.initials: J
authors.lastname: Kiyasu
authors.forename: Masanori
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nino
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Morito
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019938:Cyclin D1 / Q000032:analysis* / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis*; D020522:Lymphoma, Mantle-Cell / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: C530104:CCND1 protein, human; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27