Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer

Ashish B Rajput,Sonal Varma,Bruce E Elliott,Sandip K Sengupta,Harriet E Feilotter,Chien-Hung Chen,Yolanda Madarnas,Keyue Ding,Nianping Hu,Paul C Park,Judy-Anne W Chapman

doi:10.3390/cancers3044212

Ashish B Rajput, Sonal Varma + Show 9 more

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https://doi.org/10.3390/cancers3044212

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Journal: Cancers	Publication Date: Dec 6, 2011
Citations: 69	License type: CC BY 3.0

Affiliation: Queen's University, Cancer Care South East

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 (<50% stained nuclei). On multivariate analysis, IHC expression of CENPA showed weak association with DFS (HR > 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.

Highlights

Genomic stability depends upon equal partitioning of replicated chromosomes to daughter cells during cell division
The patients with primary breast cancer (BCa) tumors in this tissue microarray (TMA) were all managed at the Kingston Regional Cancer Centre from 2005 to 2007, after the introduction of routine human epidermal growth factor receptor-2 (HER 2) testing
Aneuploidy results from gain or loss of entire chromosomes leading to genetic instability that can progress from carcinoma in situ or pre-cancerous lesions to invasive cancer at various sites such as the colon, cervix, and esophagus [13,14,15]

Summary

Introduction

Genomic stability depends upon equal partitioning of replicated chromosomes to daughter cells during cell division. An error in chromosome segregation leading to chromosome copy number changes is known as ‘aneuploidy’. The fact that about 90% of solid tumors are aneuploid [1] underscores the importance of accurately functioning mitotic cell cycle machinery. Newly formed chromosomes are distributed between daughter cells. Errors during mitosis in somatic cells cause aneuploidy, which can lead to carcinogenesis by altering the balance of oncogenes and tumor suppressors [2]. Centromere protein –A (CENPA) is a fundamental protein unit of centromeres. It is a centromere-specific histone-H3-like variant that distinguishes centromeric from other chromatin [4,5]

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