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Abdul K Siraj,1,* Sandeep Kumar Parvathareddy,1,* Padmanaban Annaiyappanaidu,1 Saeeda O Ahmed,1 Nabil Siraj,1 Asma Tulbah,2 Fouad Al-Dayel,2 Dahish Ajarim,3 Khawla S Al-Kuraya1 1Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 2Department of Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; 3Department of Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia*These authors contributed equally to this workCorrespondence: Khawla S Al-KurayaHuman Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi ArabiaTel +966 1-205-5167Fax +966 1-205-5170Email kkuraya@kfshrc.edu.saPurpose: The cyclin D1 protein regulates cell cycle progression which is mediated by its interactions with cyclin-dependent kinases. Over-expression of cyclin D1 has been observed in several human cancers. This study was conducted to evaluate cyclin D1 expression in a large cohort of Middle Eastern breast cancers and determine its prognostic significance.Patients and Methods: Cyclin D1 expression was assessed immunohistochemically and its association with clinico-pathological parameters was analyzed in 1003 breast cancer patients.Results: Cyclin D1 was over-expressed in 59.4% (596/1003) of cases and significantly associated with a subset of breast cancers having favorable prognostic features, such as low grade (p < 0.0001), low stage (p = 0.0276), estrogen receptor (p < 0.0001) and progesterone receptor positive (p < 0.0001) tumors. An inverse association was found with triple negative breast cancers (p < 0.0001). More importantly, cyclin D1 expression was an independent predictor of favorable overall survival in our cohort (hazard ratio = 0.70; 95% confidence interval = 0.50– 0.98; p = 0.0395). Also, tumors that highly expressed cyclin D1 had a longer recurrence-free survival. However, this significant association was seen only in univariate analysis. We also found cyclin D1 to be associated with phospho-Rb in luminal subtype of breast cancer and co-expression of both these markers was an independent predictor of luminal A breast cancer.Conclusion: Our results reinforced the role of cyclin D1 in breast cancer pathology and revealed its expression as a valuable independent prognostic indicator for breast cancer from Middle Eastern ethnicity.Keywords: cyclin D1, breast cancer, prognosis, immunohistochemistry |
