title: Immunohistochemical Assessment of Expression of Centromere Protein-A (CENPA) in Human Invasive Breast Cancer.
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.
authors.affiliation: Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L 3N6, Canada. feilotth@kgh.kari.net.
authors.forename: Ashish B
authors.initials: AB
authors.lastname: Rajput
authors.forename: Nianping
authors.initials: N
authors.lastname: Hu
authors.forename: Sonal
authors.initials: S
authors.lastname: Varma
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Keyue
authors.initials: K
authors.lastname: Ding
authors.forename: Paul C
authors.initials: PC
authors.lastname: Park
authors.forename: Judy-Anne W
authors.initials: JA
authors.lastname: Chapman
authors.forename: Sandip K
authors.initials: SK
authors.lastname: Sengupta
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Madarnas
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Elliott
authors.forename: Harriet E
authors.initials: HE
authors.lastname: Feilotter