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Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer
Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
Cancer Research institute, Queen’s University, Kingston, ON K7L 3N6, Canada
NCIC Clinical Trials Group, Queen’s University, Kingston, ON K7L 3N6, Canada
Department of Oncology, Cancer Center of Southeastern Ontario, Kingston, ON K7L 2V7, Canada
* Author to whom correspondence should be addressed.
Received: 2 October 2011; in revised form: 24 November 2011 / Accepted: 30 November 2011 / Published: 6 December 2011
Abstract: Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa)—the 70 gene signature MammaPrint® and the five gene Molecular Grade Index (MGISM). Our aim was to assess the immunohistochemical (IHC) expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM) estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS). Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02) in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei) was 79% compared to 85% in low expression tumors ( 60.07; p = 0.06) within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker.
Keywords: CENPA; breast cancer; immunohistochemistry
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Rajput, A.B.; Hu, N.; Varma, S.; Chen, C.-H.; Ding, K.; Park, P.C.; Chapman, J.-A.; SenGupta, S.K.; Madarnas, Y.; Elliott, B.E.; Feilotter, H.E. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer. Cancers 2011, 3, 4212-4227.
Rajput AB, Hu N, Varma S, Chen C-H, Ding K, Park PC, Chapman J-A, SenGupta SK, Madarnas Y, Elliott BE, Feilotter HE. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer. Cancers. 2011; 3(4):4212-4227.
Rajput, Ashish B.; Hu, Nianping; Varma, Sonal; Chen, Chien-Hung; Ding, Keyue; Park, Paul C.; Chapman, Judy-Anne W.; SenGupta, Sandip K.; Madarnas, Yolanda; Elliott, Bruce E.; Feilotter, Harriet E. 2011. "Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer." Cancers 3, no. 4: 4212-4227.