Cyclin D1 (bcl-1)

Dako (DCS-6), Immunotech (5D4) and Novocastra (P2D11F11, DCS-6).

Clone DCS-6 is effective on paraffin wax-embedded tissue. We have found that microwave antigen unmasking in Tris buffer produces an optimum immunoreaction. Other laboratories have found the strongest staining intensity with lowest background staining was achieved when both microwave and sonication-induced epitope retrieval methods were used.

The G1 cyclin gene, cyclin D1 (PRAD-1, CCND-1), located on chromosome 11q13 (Motokura et al, 1991), exhibits characteristics of known cellular oncogenes (Schuuring et al, 1992). It plays an integral role in normal cell growth control and a complementary role in the in vitro transformation of cultured cells (Hinds et al, 1994; Hirama & Koeffler, 1995). Mechanisms of abnormal 11q13 regulation leading to cyclin D1 overexpression include genomic amplification in a variety of carcinomas (Proctor et al, 1991; Foulkes et al, 1993; Karlseder et al, 1994), characteristic t(11;14) (q13; q32) reciprocal chromosomal translocations in mantle cell lymphoma (Williams et al, 1991; Ott et al, 1996; Brynes et al, 1997) and chromosome 11 pericentric inversions in parathyroid adenomas. Together, cyclin D1 and cyclin-dependent kinase (Cdk) activities are required for completion of the G1/S transition in the normal mammalian cell cycle (Bartkova et al, 1994). Further, cyclin D1 inhibits the growth suppressive function of retinoblastoma tumorsuppressor protein (Ewen et al, 1993). Cyclin D1 is a 36 kD protein with a maximum expression of cyclin D1 occurring at a critical point in mid to late G1 phase of the cell cycle. Recombinant prokaryotic fusion protein is used as the antigen to raise antibody to cyclin D1 (class IgG2a). In normal tissues, cyclin D1 expression is restricted to the proliferative zone of epithelial tissues and is absent from several other tissues such as lymph node, spleen and tonsil.

Many neoplasms, including mantle cell lymphoma, parathyroid adenomas and a spectrum of carcinomas including breast, supradiaphragmatic squamous cell, ovarian and bladder transitional cell carcinomas demonstrate overexpression of cyclin D1 antibody on paraffin sections. Immunohistochemical demonstration of nuclear cyclin D1 protein was observed in 75% of mantle cell lymphoma and was not found in normal B cells and other B-cell lymphomas (including follicle center cell lymphoma, diffuse large B-cell lymphoma, lymphocytic lymphoma and MALT lymphoma) (Ott et al, 1996).

Cyclin D1 is useful to distinguish mantle cell lymphoma from the other low grade B-cell lymphomas. Breast cancer tissue may be used as a positive control.

•Bartkova J, Lukas J, Strauss M, Bartek J 1994 Cell cycle-related variation and tissue-restricted expression of human cyclin D1 protein. Journal of Pathology 172:237-245.

•Brynes RK, McCourty A, Tamayo R, Jenkins K, Battifora H 1997 Demonstration of Cyclin D1 (Bcl-1) in mantle cell lymphoma. Enhanced staining using heat and ultrasound epitope retrieval. Applied Immunohistochemistry 5: 45-48.

•Ewen ME, Sluss HK, Sherr CJ, Matsushime H, Kato J, Livingston DM 1993 Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. Cell 73:487-497.

•Foulkes WD, Campbell IG, Stamp GWH, Trowsdale J 1993 Loss of heterozygosity and amplification on chromosome 11q in human ovarian cancer. British Journal of Cancer 67: 268-273.

•Hinds PW, Dowdy SF, Eaton EN, Arnold A, Weinberg RA 1994 Function of a human cyclin gene as an oncogene. Proceedings of the National Academy of Science USA 91:709-713.

•Hirama T, Koeffler HP 1995 Role of the cyclin-dependent kinase inhibitors in the development of cancer. Blood 86:841-854.

•Karlseder J, Zeillinger R, Schneeberger C et al 1994 Patterns of DNA amplification at band q13 of chromosome 11 in human breast cancer. Genes, Chromosomes and Cancer 9:42-48.

•Motokura T, Bloom T, Kim HG et al 1991 A novel cyclin encoded by a bcl-1-linked candidate oncogene. Nature 350:512-515.

•Ott MM, Helbing A, Ott G, Bartek J et al 1996 bcl-1 rearrangement and cyclin D1 protein expression in mantle cell lymphoma. Journal of Pathology 179: 238-242.

•Proctor AJ, Combs LM, Cairns JP, Knowles MA 1991 Amplification at chromosome 11q13 in transitional cell tumors of the bladder. Oncogene 6:789-795.

•Schuuring E, Verhoeven E, Mooi WJ, Michalides RJ 1992 Identification and cloning of two overexpressed genes, U21B31/PRADI and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene 7: 355-361.

•Williams ME, Meeker TC, Swerdlow SH 1991 Rearrangement of the chromosome 11 bcl-1 locus in centrocytic lymphomas: analysis with multiple breakpoint probes. Blood 78:493-498.

Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.