Cyclin D1

Synonyms: PRAD-1, CCND-1, BCL-1

by Jan Klos

Background

Cyclins are regulatory subunits of the cyclin dependent kinases (CDK). The temporary expression of cyclins is related to control of different specific phases of the cell cycle. Cyclin D1 is a 36 kD protein which plays an important role in normal cell growth control. Cyclin D1 is encoded on chromosome 11q13 by the gene known as PRAD-1, CCND-1 or BCL-1. It is needed for completion of the G1/S transition in normal cells. It inhibits also the suppressive function of retinoblastoma tumor suppressor protein (Rb). The maximum of Cyclin D1 expression is middle to late G1 phase of the cell cycle.  In normal mammalian epithelial tissues the expression of Cyclin D1 is limited only to proliferative zone.

Expression in normal cells

Immunoreactivity for cyclins is localized to nuclei of proliferating normal cells.

Expression in tumors

Cyclin D1 is typically overexpressed in cases of Mantle Cell Lymphoma (MCL) as a result of chromosomal translocation t(11;14)(q13;q32). Single Cyclin D1 negative cases of MCL are usually positive for SOX11. Majority of cases of Hairy Cell Leukemia (about 75%) show usually moderate nuclear positivity. About 40% of parathyroid adenoma is also positive as a result of pericentric inversion of chromosome 11. About 10-15% of plasmacytomas harbor translocation t(11;14) and as a result are also positive for Cyclin D1. These cases show often expression of CD20 and PAX5. There is some evidence that plasmacytomas with this translocation may have more aggressive clinical course. No expression of Cyclin D1 is found in normal B cells or other malignant lymphomas. Increased number of Cyclin D1 positive cells in proliferation centers in chronic lymphatic leukemia is related to increased number of proliferating cells and not chromosomal aberrations. Some reports demostrate positivity for Cyclin D1 among DLBCL cases mostly negative for CD5 and without alterations of CNNd1 gene. A variety of carcinomas also show positive staining (including breast carcinoma, transitional cell carcinoma of the urinary bladder, papillary thyroid carcinoma, endometrioid carcinoma, some carcinoid tumors, supradiaphragmatic squamous cell carcinomas etc.) most often as a result of genomic amplifications. Overexpression of Cyclin D1 correlates often with poorer prognosis according to some papers which may at least partially reflect the involvement of the protein in the cell cycle. The IHC staining for Cyclin D1 used to be one of most difficult in paraffin embedded material, because of varying levels of antigen expression and low sensitivity of available antibodies before the era of  the highly specific and sensitive monoclonal rabbit antibodies  directed against the new epitopes available at the begining of the 20th century.
Gardner type fibroma 100%

need to control data

 need to control data

Staining pattern

Staining pattern is nuclear.

Control tissue

Control tissue is tonsil.

Application

  • Is important member of diagnostic panel for malignant lymphoma
  • In some solid tumors shows correlation with prognosis

Selected references

  1. Coffin CM1, Hornick JL, Zhou H, et al. Gardner fibroma: a clinicopathologic and immunohistochemical analysis of 45 patients with 57 fibromas. Am J Surg Pathol. 2007 Mar;31(3):410-6.
  2. https://app.immunoquery.com
  3. https://en.wikipedia.org/wiki/Cyclin D
  4. https://www.nordiqc.org
  5. Lee CH1, Ali RH, Rouzbahman M, et al. Cyclin D1 as a diagnostic immunomarker for endometrial stromal sarcoma with YWHAE-FAM22 rearrangement. Am J Surg Pathol. 2012 Oct;36(10):1562-70.
  6. Sherman MJ, Hanson CA, Hoyer JD. An assessment of the usefulness of immunohistochemical stains in the diagnosis of hairy cell leukemia. Am J Clin Pathol. 2011 Sep;136(3):390-9. doi: 10.1309/AJCP5GE1PSBMBZTW.
  7. Vela-Chávez T1, Adam P, Kremer M, et al. Cyclin D1 Positive Diffuse Large B-cell Lymphoma Is a Post-Germinal Center-Type Lymphoma Without Alterations in the CCND1 Gene Locus Leuk Lymphoma 2011 Mar;52(3):458-66. doi: 10.3109/10428194.2010.540361. Epub 2011 Feb 1. 
  8. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 2017 4th Edition
  9. Zeng W1, Fu K, Quintanilla-Fend L, et al. Cyclin D1-negative blastoid mantle cell lymphoma identified by SOX11 expression. Am J Surg Pathol. 2012 Feb;36(2):214-9. doi: 10.1097/PAS.0b013e318241f050.