Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 Dec;85(12):1270–1279. doi: 10.1111/j.1349-7006.1994.tb02940.x

Immunohistochemical Analysis of Cyclin D1 Protein in Hematopoietic Neoplasms with Special Reference to Mantle Cell Lymphoma

Shigeo Nakamura 1,✉, Masao Seto 3, Shogo Banno 3,5, Susumu Suzuki 6, Takashi Koshikawa 1, Kuniyoshi Kitoh 1, Yoshitoyo Kagami 2, Michinori Ogura 2, Yasushi Yatabe 7, Masaru Kojima 8, Tadashi Motoori 9, Toshitada Takahashi 4, Ryuzo Ueda 3, Taizan Suchi 1
PMCID: PMC5919397  PMID: 7531681

Abstract

Immunohistochemical expression of PRAD1/cyclin D1 protein has been investigated in 106 tissue specimens of 104 cases of lymphoma, non‐neoplastic lymphoid disorders and other hematologic malignancies by employing the monoclonal antibody 5D4 with formalin‐fixed paraffin‐embedded sections, using the microwave oven heating method. Positive neoplastic cells were found in 60 (74%) of 81 cases of non‐Hodgkin's lymphoma. The positivity pattern was nuclear in 17 (85%) of 20 cases of mantle cell lymphoma in which cytoplasmic staining was also seen. This pattern of cyclin D1 positivity was in contrast to the negative staining of normal reactive mantle zones. In the other cases, positivity appeared to lie within the cell cytoplasm without nuclear staining, and most of the nodal follicular and diffuse B‐cell lymphomas variously expressed PRAD1/cyclin D1. In contrast, the reaction was absent in a significant number of T‐cell and extranodal B‐cell lymphomas. Immunolocalization of PRAD1/cyclin D1 expression appears to be a useful diagnostic adjunct to discriminate mantle cell lymphoma from other non‐Hodgkin's lymphomas.

Keywords: Malignant lymphoma –PRAD1, BCL‐1, Cyclin D1 protein, Immuno histochemistry

Full Text

The Full Text of this article is available as a PDF (774.4 KB).

REFERENCES

  • 1. ) Banks , P. M. , Chan , J. , Cleary , M. L. , Delsol , G. , De Wolf‐Peeters , C. , Gatter , K. , Grogan , T. M. , Harris , N. L. , Isaacson , P. G. , Jaffe , E. S. , Mason , D. Y. , Pileri , S. , Ralfkiaer , E. , Stein , H. and Warnke , R. A.Mantle cell lymphoma: a proposal for unification of morphologic, immunologic, and molecular data . Am. J. Surg. Pathol , 16 , 637 – 640 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Jaffe , E. S. , Raffeld , M. , Medeiros , L. J. and Stetler‐Stevenson , M.An overview of the classification of non‐Hod gkin's lymphomas: an integration of morphological and phenotypical concepts . Cancer Res. 52 , 5447s – 5452s ( 1992. ). [PubMed] [Google Scholar]
  • 3. ) Weisenburger , D. D. and Chan , W. C.Lymphomas of follicles. Mantle cell and follicular center cell lymphomas . Am. J. Clin. Pathol , 9 , 409 – 420 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Jaffe , E. S. , Bookman , M. A. and Longo , D. L.Lymphocytic lymphoma of intermediate differentiation– mantle zone lymphoma. A distinct subtype of B‐cell lymphoma . Hum. Pathol. , 18 , 877 – 880 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Berard , C. W.Reticuloendothelial system: an overview of neoplasia . In “ The Reticuloendothelial System, ” ed. Rebuck J. W. , Berard C. W. and Abell M. R. , pp. 301 – 317 ( 1975. ). Williams & Wilkins; , Baltimore . [Google Scholar]
  • 6. ) Lennert , K. and Feller , A. C. “ Histopathology of Non‐Hodgkin's Lymphoma ” ( 1992. ). Springer Verlag; , Berlin . [Google Scholar]
  • 7. ) Weisenburger , D. D. , Kim , H. and Rappaport , H.Mantle‐zone lymphoma: a follicular variant of intermediate lymphocytic lymphoma . Cancer , 49 , 1429 – 1438 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Tsujimoto , Y. , Yunis , J. , Onorato‐Showe , L. , Elikson , J. , Nowell , P. C. and Croce , C. M.Molecular cloning of the chromosomal breakpoint of B‐cell lymphomas and leukemias with the t(11;14) chromosome translocation . Science , 224 , 1403 – 1406 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Medeiros , L. J. , van Krieken , J. H. , Jaffe , E. S. and Raffeld , M.Association of bcl‐1 rearrangements with lymphocytic lymphoma of intermediate differentiation . Blood , 16 , 2086 – 2090 ( 1990. ). [PubMed] [Google Scholar]
  • 10. ) Raffeld , M. and Jaffe , E. S.BCL‐1, t(ll;14), and mantle cell‐derived lymphomas . Blood , 76 , 2086 – 2090 ( 1990. ). [PubMed] [Google Scholar]
  • 11. ) Williams , M. E. , Swerdlow , S. H. , Rosenberg , C. L. and Arnold , A.Characterization of chromosome 11 translocation breakpoint at the bcl‐1 and PRAD1 loci in centrocytic lymphoma . Cancer Res. , 52 , 5541s – 5544s ( 1992. ). [PubMed] [Google Scholar]
  • 12. ) Arnold , A. , Kim , H. G. , Gaz , R. D , Eddy , R. L. , Fukushima , Y. , Byers , M. G. , Shows , T. B. and Kronenberg , H. M.Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma . J Clin. Invest. , 83 , 2034 – 2040 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Motokura , T. , Bloom , T. , Kim , H. G. , Juppner , H. , Ruderman , J. V. , Kronenberg , H. M. and Arnold , A.A novel cyclin encoded by a bcl1‐Iinked candidate oncogene , Nature , 350 , 512 – 515 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Rosenberg , C. L. , Kim , H. G. , Shows , T. B. , Kronenberg , H. M. and Arnold , A.Rearrangement and overexpression of D11S287E, a candidate oncogene on chromosome 11ql3 in benign parathyroid tumors . Oncogene , 6 , 449 – 453 ( 1991. ). [PubMed] [Google Scholar]
  • 15. ) Withers , D. A. , Harvey , R. C. , Faust , J. B. , Melnyk , O. , Carey , K. and Meeker , T. C.Characterization of a candidate bcl‐1 gene . Mol Cell Biol , 11 , 4846 – 4853 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. ) Rosenberg , C. L. , Wong , E. , Petty , E. M. , Bale , A. E. , Tsujimoto , Y. , Harris , N. L. and Arnold , A.PRAD1, a candidate BCL‐1 oncogene: mapping and expression in centrocytic lymphoma . Proc. Natl. Acad. Sci USA , 88 , 9638 – 9642 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Seto , M. , Yamamoto , K. , Lida , S. , Akao , Y. , Utsumi , K. , Kubonishi , I. , Miyoshi , I. , Ohtsuki , T. , Yawata , Y. , Namba , M. , Motokura , T. , Arnold , A. , Takahashi , T. and Ueda , R.Gene rearrangement and overexpression of PRAD1 in lymphoid malignancy with the t(ll;14) (q13;q23) translation , Oncogene , 7 , 1401 – 1406 ( 1992. ). [PubMed] [Google Scholar]
  • 18. ) Komatsu , H. , Yoshida , K. , Seto , M. , Lida , S. , Aikawa , T. , Ueda , R. and Mikuni , C.Overexpression of PRAD1 in a mantle zone lymphoma patient with a t(ll;22)(ql3;qll) translocation . Br. J. Haematol. , 85 , 427 – 429 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Komatsu , H. , Iida , S. , Yamamoto , K. , Mikuni , C. , Nitta , M. , Takahashi , T. , Ueda , R. and Seto , M. Avariant chromosome translocation at Ilql3 identifying PRADI/ cyclinDl astheBCL-1 gene .Blood , 84 , 1226 – 1231 ( 1994. ). [PubMed] [Google Scholar]
  • 20. ) Oka , K. , Ohno , T. , Kita , K. , Yamaguchi , M. and Takakura , N.PRAD1 gene over‐expression in mantle‐cell lymphoma but not in other low‐grade B‐cell lymphomas, including extranodal lymphoma . Br. J. Haematol. , 86 , 786 – 791 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Banno , S. , Yoshikawa , K. , Nakamura , S. , Yamamoto , K. , Seito , T. , Nitta , M. , Takahashi , T. , Ueda , R. and Seto , M.Monoclonal antibody against PRAD1/cyclin D1 stains nuclei of tumor cells with translocation or amplification at BCL‐1 locus . Jpn. J. Cancer Res. , 85 , 918 – 926 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. ) The non‐Hodgkin's Lymphoma Pathologic Classification Project: National Cancer Institute sponsored study of classification of non‐Hodgkin's lymphomas. Summary and description of a working formulation for clinical usage . Cancer , 49 , 2112 – 2135 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Hsu , S. M. , Raine , L. and Fanger , H.The use of avidinbiotin‐peroxidase complex (ABC) in immunoperoxidase technique: a comparison between ABC and unlabeled antibody (PAP) procedures . J. Histochem. Cytochem. , 29 , 577 – 580 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Delellis , R. A. , Sternberger , L. A. , Mann , R. B. , Banks , P. M. and Nakane , P. K.Immunoperoxidase technics in diagnostic pathology: report of a workshop sponsored by the National Cancer Institute . Am. J. Clin. Pathol , 71 , 483 – 488 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Shi , S. R. , Key , M. E. and Kalra , K. L.Antigen retrieval in formalin‐fixed, paraffin‐embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections . J Histochem. Cytochem. , 39 , 741 – 748 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Sheibani , K. , Burke , J. S. , Swartz , W. G. , Nademanee , A. and Winberg , C. D.Monocytoid B‐cell lymphoma: clinicopathologic study of 21 cases of a unique type of low‐grade lymphoma . Cancer , 62 , 1531 – 1538 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Isaacson , P. G. and Spencer , J.Malignant lymphoma of mucosa‐associated lymphoid tissue . Histopathology , 11 , 445 – 462 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 28. ) Harris , N. L.Extranodal lymphoid infiltrates and mucosa‐associated lymphoid tissue (MALT): a unifying concept . Am. J. Surg. Pathol. , 15 , 879 – 884 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Baldin , V. , Lukas , J. , Marcote , M. J. , Pagano , M. and Draetta , G.Cyclin D1 is a nuclear protein required for cell cycle progression in Gl . Genes Dev. , 7 , 812 – 821 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 30. ) Hinds , P. W. , Dowdy , S. P. , Eaton , E. N. and Arnold , A.Function of a human cyclin as an oncogene. Proc . Natl. Acad. Sci. USA , 91 , 709 – 713 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. ) Marx , J.How cells cycle towards cancer . Science , 263 , 319 – 321 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 32. ) Gillett , C. , Fantl , V. , Smith , R. , Fisher , C. , Bartek , J. , Dickson , C. , Barnes , D. and Peters , G.Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining . Cancer Res. , 54 , 1812 – 1817 ( 1994. ). [PubMed] [Google Scholar]
  • 33. ) Bodrug , S. E. , Warner , B. J. , Bath , M. L. , Lindeman , G. J. , Harris , A. W. and Adams , J. M.Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomatogenesis with the myc gene . EMBO J. , 13 , 2124 – 2130 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES