Analysis of cyclins A, B1, D1 and E in breast cancer in relation to tumour grade and other prognostic factors

BackgroundThe cell cycle is promoted by activation of cyclin dependent kinases (Cdks), which are regulated positively by cyclins and negatively by Cdk inhibitors. Proliferation of carcinoma is associated with altered regulation of the cell cycle. Little is known on the combined alterations of cyclins A, B1, D1 and E in breast cancer in relation to the tumour grade and other prognostic factors.FindingsImmunohistochemical analysis of cyclins A, B1, D1 and E, estrogen receptor, progesterone receptor, Ki-67, Her-2/neu and CK5/6 was performed on 53 breast carcinomas. mRNA levels of the cyclins were analysed of 12 samples by RT-PCR. The expression of cyclins A, B1 and E correlated with each other, while cyclin D1 correlated with none of these cyclins. Cyclins A, B1 and E showed association with tumour grade, Her-2/neu and Ki-67. Cyclin E had a negative correlation with hormone receptors and a positive correlation with triple negative carcinomas. Cyclin D1 had a positive correlation with ER, PR and non-basal breast carcinomas.ConclusionCyclin A, B1 and E overexpression correlates to grade, Ki-67 and Her2/neu expression. Overexpression of cyclin D1 has a positive correlation with receptor status and non-basal carcinomas suggesting that cyclin D1 expression might be a marker of good prognosis. Combined analysis of cyclins indicates that cyclin A, B and E expression is similarly regulated, while other factors regulate cyclin D1 expression. The results suggest that the combined immunoreactivity of cyclins A, B1, D and E might be a useful prognostic factor in breast cancer.

[1]  K. Jirström,et al.  Adverse effect of adjuvant tamoxifen in premenopausal breast cancer with cyclin D1 gene amplification. , 2005, Cancer research.

[2]  M. Peters,et al.  Prognostic value of cell cycle regulator molecules in surgically resected stage I and II breast cancer. , 2004, Oncology reports.

[3]  T. Hwang,et al.  Prognostic value of combined analysis of cyclin D1 and estrogen receptor status in breast cancer patients , 2003, Pathology international.

[4]  O. Barbash,et al.  SCF(Fbx4/alphaB-crystallin) E3 ligase: when one is not enough. , 2008, Cell cycle.

[5]  D. Germain,et al.  Tamoxifen stimulates the growth of cyclin D1-overexpressing breast cancer cells by promoting the activation of signal transducer and activator of transcription 3. , 2008, Cancer research.

[6]  H. Nevanlinna,et al.  Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer , 2008, Breast Cancer Research and Treatment.

[7]  O. Fadare,et al.  Clinical and pathologic aspects of basal-like breast cancers , 2008, Nature Clinical Practice Oncology.

[8]  H. Nevanlinna,et al.  High cyclin B1 expression is associated with poor survival in breast cancer , 2009, British Journal of Cancer.

[9]  L. Rydén,et al.  Cyclin D1 overexpression is a negative predictive factor for tamoxifen response in postmenopausal breast cancer patients , 2004, British Journal of Cancer.

[10]  A. Hautamäki,et al.  The national research and development centre for welfare and health. , 1993 .

[11]  A. Thompson,et al.  Cyclin D1 and breast cancer. , 2006, Breast.

[12]  L. Skoog,et al.  Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance , 2005, Breast Cancer Research and Treatment.

[13]  M. Barbacid,et al.  Cell cycle, CDKs and cancer: a changing paradigm , 2009, Nature Reviews Cancer.

[14]  Jeffrey E. Green,et al.  Molecular Profiling in Breast Cancer , 2006 .

[15]  Isabelle Bedrosian,et al.  Cyclin E and survival in patients with breast cancer. , 2002, The New England journal of medicine.

[16]  A. Bednarek,et al.  Cyclin E expression in operable breast cancer quantified using real-time RT-PCR: a comparative study with immunostaining. , 2006, Japanese journal of clinical oncology.

[17]  M. Fernö,et al.  Expression of cyclins E, A, and B, and prognosis in lymph node‐negative breast cancer , 2003, The Journal of pathology.

[18]  S. Inoue,et al.  Nuclear cyclin B1 in human breast carcinoma as a potent prognostic factor , 2007, Cancer science.

[19]  O. Topolcan,et al.  The importance of prognostic factors in premenopausal women with breast cancer. , 2007, Anticancer research.

[20]  H. Nevanlinna,et al.  Ki67 and cyclin A as prognostic factors in early breast cancer. What are the optimal cut‐off values? , 2007, Histopathology.

[21]  A. Tutt,et al.  Triple negative tumours: a critical review , 2007, Histopathology.

[22]  O. Barbash,et al.  SCFFbx4/αB-crystallin E3 ligase: When one is not enough , 2008 .

[23]  C. Blomqvist,et al.  Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer , 2005, British Journal of Cancer.

[24]  A. Bednarek,et al.  Cyclin E expression in breast cancer correlates with negative steroid receptor status, HER2 expression, tumor grade and proliferation. , 2006, Journal of experimental & clinical cancer research : CR.