Cyclin D1 (PRAD-1, bcl-1, CCND1)

This gene was first identified from parathyroid adenomas and designated PRAD1 (parathyroid adenomatosis)16,17. Cyclin D1 and cyclin D3 have similar roles in the regulation of the G1 check-point of the cell cycle2, acting via phosphorylation of the retinoblastoma gene product6 . The gene locus is on 11q6. The gene is overexpressed in mantle cell lymphomas due to a chromosomal rearrangement t(11;14)(q13;q32)20. This translocation can be demonstrated with high sensitivity by FISH14,15.

Specific staining is nuclear. The antibodies against cyclin D1 have fastidious requirements3. A newly available monoclonal rabbit antibody is reported to to give consistent immunoreactivity, compared with the previously available mouse monoclonal antibody9.

Immunohistochemical expression

Lymphoid cells of normal lymph node, spleen and tonsil are negative for cyclin D111.

 

Staining in a number of B-cell neoplasms has been reported using a rabbit monoclonal antibody, which has a greater sensitivity than does the mouse monoclonal antibody9:

 

Mantle cell lymphoma

18/1911, 10/1012, 15/1913, 12/1218, 23/3219, 15/1521

 

Mantle cell lymphoma-like, CD5-

0/311

 

Blastoid mantle cell lymphoma

3/310

 

Myeloma

1/2222

 

Hairy cell leukaemia

1/519, 1/1522

 

CLL/SLL

0/911, 3/1612 , 0/1218, 1/1819, 1/721, 0/1822

 

DLBCL

0/911, 0/3322

 

Follicular lymphoma

0/1411, 0/1119, 0/1021

 

Extranodal MALT lymphoma

0/411, 0/421

 

Splenic marginal zone lymphoma

0/219

 

Burkitt's lymphoma

 0/922

 

Precursor T-cell Lymphoblastic lymphoma

0/422

 

Adult T-cell lymphoma/leukaemia

0/122

 

Reactive lymphoid hyperplasia

0/721

 

staining score = score for percentage positive cells x intensity score

 

 

reference 9 

staining score

 
 

0

1-4

6-8

9-12

 

Mantle cell lymphoma (including two CD5- cases)

mouse MAb

1/25

15/25

7/25

2/25

rabbit MAb

0/30

8/30

9/30

13/30

Myeloma

rabbit MAb

9/12

1/12

1/12

1/12

Hairy cell leukaemia

rabbit MAb

3/5

2/5

0/5

0/5

CLL/SLL

rabbit MAb

13/15

1/15

0/15

1/15

DLBCL

rabbit MAb

25/25

 

 

 

Follicular lymphoma

rabbit MAb

10/10

 

 

 

Extranodal MALT lymphoma

rabbit MAb

14/14

 

 

 

Nodal marginal zone lymphoma

rabbit MAb

1/1

 

 

 

Lymphoplasmacytic lymphoma

rabbit MAb

1/1

 

 

 

Lymphoblastic lymphoma

rabbit MAb

2/2

 

 

 

Extranodal NK/T-cell lymphoma

rabbit MAb

13/13

 

 

 

Peripheral T-cell lymphoma NOS

rabbit MAb

6/6

 

 

 

Anaplastic large cell lymphoma

rabbit MAb

1/1

 

 

 

Angioimmunoblastic T-cell lymphoma

rabbit MAb

1/1

 

 

 

PTLD

rabbit MAb

1/1

 

 

 

Hodgkin lymphoma

rabbit MAb

4/4

 

 

 

Reactive lymphoid hyperplasia

rabbit MAb

9/9

 

 

 

staining score = score for percentage positive cells x intensity score

There was less background staining with the rabbit monoclonal antibody.

Diagnostic utility

Cyclin D3

There is recent evidence that cyclin D3 may be expressed differentially among lymphoma subtypes and overexpression may be associated with a poor outcome8.

References

1 Mishina, T. Dosaka-Akita, H. Kinoshita, I. Cyclin D1 expression in non-small-cell lung cancers: its association with altered p53 expression, cell proliferation and clinical outcome. Br J Cancer 1999;80:1289-95.

2 SCC Wong et al. Differential expression of p16/p21/p27 and cyclin D1/D3, and their relationship to cell proliferation, apoptosis and tumour progression invasive ductal carcinoma of the breast. J Pathol 2001;194:35-42

3 Chan, J. K., Miller, K. D., Munson, P., Isaacson, P. G. Immunostaining for cyclin D1 and the diagnosis of mantle cell lymphoma: is there a reliable method? Histopathology 1999;34:266-268.

4 McDonald, J. W., Pilgram, T. K. Nuclear expression of p53, p21 and cyclin D1 is increased in bronchioloalveolar carcinoma Histopathology 1999;34:439-446.

5 Yatabe, Y., Suzuki, R., Matsuno, Y. et al. Morphological spectrum of cyclin D1-positive mantle cell lymphoma: study of 168 cases. Pathol Int 2001;51:747-61.

6 Walton S-J, Freakins RM. Expression of retinoblastoma, p16 and cyclin D1 genes in gastric adenocarcinomas and precarcinomatous lesions. Pathological Society July 2002, abstract 131.

7 Matutes E. New additions to antibody panels in the characterisation of chronic lymphoproliferative disorders. J Clin Pathol 2002;55:180-183.

8 Leoncini, L., Lazzi, S., Bellan, C. and Tosi, P. Cell kinetics and cell cycle regulation in lymphomas. J Clin Pathol 2002;55:648-55.

9 Cheuk, W., K. O. Wong, et al. Consistent immunostaining for cyclin D1 can be achieved on a routine basis using a newly available rabbit monoclonal antibody. Am J Surg Pathol 2004;28(6): 801-7.

10 Aguilera NS, Uusafr M, Wenig BM, et al. The blastic variant of mantle cell lymphoma arising in Waldeyer's tonsillar ring. J Laryngol Otol 1998; 112:991-4

11 de Boer CJ, Schuuring E, Dreef E, et al. Cyclin D1 protein analysis in the diagnosis of mantle cell lymphoma. Blood 1995; 86:2715-23 FULL TEXT

12 de Leon ED, Alkan S, Huang JC, et al. Usefulness of an immunohistochemical panel in paraffin-embedded tissues for the differentiation of B-cell non-Hodgkin's lymphomas of small lymphocytes. Mod Pathol 1998; 11:1046-51

13 Kuroda H, Komatsu H, Nakamura S, et al. The positive nuclear staining observed with monoclonal antibody against PRAD1/cyclin D1 correlates with mRNA expression in mantle cell lymphoma. Jpn J Cancer Res 1995; 86:890-8

14 Li JY, Gaillard F, Moreau A, et al. Detection of translocation t(11;14)(q13;q32) in mantle cell lymphoma by fluorescence in situ hybridization. Am J Pathol 1999; 154:1449-52 FULL TEXT

15 Monteil M, Callanan M, Dascalescu C, et al. Molecular diagnosis of t(11;14) in mantle cell lymphoma using two-colour interphase fluorescence in situ hybridization. Br J Haematol 1996; 93:656-60

16 Motokura T, Bloom T, Kim HG, et al. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature 1991; 350:512-5

17 Rosenberg CL, Wong E, Petty EM, et al. PRAD1, a candidate BCL1 oncogene: mapping and expression in centrocytic lymphoma. Proc Natl Acad Sci U S A 1991; 88:9638-42

18 Singh N,Wright DH. The value of immunohistochemistry on paraffin wax embedded tissue sections in the differentiation of small lymphocytic and mantle cell lymphomas. J Clin Pathol 1997; 50:16-21 FULL TEXT

19 Vasef MA, Medeiros LJ, Koo C, et al. Cyclin D1 immunohistochemical staining is useful in distinguishing mantle cell lymphoma from other low-grade B-cell neoplasms in bone marrow. Am J Clin Pathol 1997; 108:302-7

20 Williams ME, Swerdlow SH, Rosenberg CL, et al. Chromosome 11 translocation breakpoints at the PRAD1/cyclin D1 gene locus in centrocytic lymphoma. Leukemia 1993; 7:241-5

21 Yang WI, Zukerberg LR, Motokura T, et al. Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia. Am J Pathol 1994; 145:86-96

22 Zukerberg LR, Yang WI, Arnold A, et al. Cyclin D1 expression in non-Hodgkin's lymphomas. Detection by immunohistochemistry. Am J Clin Pathol 1995; 103:756-60

This page last revised 28.10.2006.

 

©SMUHT/PW Bishop