Invasive breast carcinomas in Ghana: high frequency of high grade, basal-like histology and high EZH2 expression

Abstract

Breast cancer in African-American women has a worse outcome than in Caucasian women. The ancestors of most African-American women come from West Africa, including Ghana. The Polycomb group protein EZH2 is a marker of poor outcome in breast cancers from Caucasian women. The histopathological features and biomarker expression of African breast cancers remain obscure. Here, we investigated a cohort of Ghanaian breast cancers to better define the prevalent tumor types and to test if EZH2 protein may identify aggressive tumors. A group of 169 breast tissues (100 invasive carcinomas and 69 benign) from women treated at Komfo Anoyke Teaching Hospital between 2006 and 2011 were histologically classified and investigated for EZH2 expression. EZH2 nuclear expression we defined as high or low following previously published criteria. Of the 100 invasive carcinomas, 89 % were ductal, 2 % were lobular, and 9 % were metaplastic. Basal-like pathological features were present in 30 % of the tumors. Of the invasive carcinomas, 7 % were grade 1, 41 % grade 2, and 52 % grade 3. EZH2 protein was overexpressed in invasive carcinomas compared to benign breast (p < 0.0001). In invasive carcinomas nuclear EZH2 overexpression was significantly associated with basal-like subtype (p = 0.03) and high histologic grade (p < 0.05). Cytoplasmic EZH2, which has not been previously reported, was present in 16 % of invasive carcinomas and it was associated with triple negative status (p = 0.02). Our results provide the first comprehensive histopathological study of this patient population and uncover the association of EZH2 with high grade and basal-like tumors. We provide the basis for further detailed investigations on this cohort to advance diagnosis and treatment of African and African-American women.

Clinical and prognostic relevance of EZH2 in breast cancer: A meta-analysis

“…In other word, tissues with poorly differentiated, ER negative, invasive HER-2 enriched, or TNBC were frequently with the abundance of EZH2. Besides, increased EZH2 expression could precede high frequencies of cell proliferation and the cell would analysis showed that impaired proliferation and metastasis were characteristically observed after knockdown of EZH2 [18,31,34]. In 2013, Knudsen et al found that high EZH2 level was associated with the risk of an ipsilateral breast event and the recurrence of ductal carcinoma in situ [35].…”

“…11 literatures which published from 2003 to 2014 were included in our meta-analysis [12][13][14][15][16][17][18][19][20][21][22] (Fig. 1).…”

“…1). 9 studies provided the integrated original information of the relationships between EZH2 expression and clinicopathological parameters in BC patients directly [12,[15][16][17][18][19][20][21][22]. 6 articles assessed the prognostic value of EZH2 (OS) in BC patients by Kaplan-Meier method [12][13][14][15]20,21].…”

Writing and Rewriting the Epigenetic Code of Cancer Cells: From Engineered Proteins to Small Molecules

“…In many cases, mutations or disruption in gene expression of the chromatin modifiers themselves have been identified. For example, the polycomb group of methyltransferases, such as enhancer of zeste homolog 2 (drosophila), are often overexpressed in basal-like breast cancers, particularly in African-American women (Chase and Cross, 2011;Pang et al, 2012). The histone methyltransferase G9a and other lysine methyltransferases have also been associated with tumorigenesis and targeted by screening and structure-based design for the identification of specific inhibitors (Unoki, 2011).…”

Cultural and Environmental Factors of Triple-Negative Breast Carcinomas

“…Among cancer mortalities, breast cancer is the second leading cause of deaths among women in the United States [2]. Though white American women have higher rates of breast cancer incidence than African American women, the latter population is more likely to die from breast cancer than any other ethnic group in the United States [3][4][5][6] .…”