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Published in: Breast Cancer Research and Treatment 1/2012

01-08-2012 | Preclinical Study

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

Authors: Judy Pang, Kathy A. Toy, Ken A. Griffith, Baffour Awuah, Solomon Quayson, Lisa A. Newman, Celina G. Kleer

Published in: Breast Cancer Research and Treatment | Issue 1/2012

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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.
Literature
1.
go back to reference Smigal C et al (2006) Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin 56(3):168–183PubMedCrossRef Smigal C et al (2006) Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin 56(3):168–183PubMedCrossRef
2.
go back to reference Eley JW et al (1994) Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study. JAMA 272(12):947–954PubMedCrossRef Eley JW et al (1994) Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study. JAMA 272(12):947–954PubMedCrossRef
3.
go back to reference Smith-Bindman R et al (2006) Does utilization of screening mammography explain racial and ethnic differences in breast cancer? Ann Intern Med 144(8):541–553PubMed Smith-Bindman R et al (2006) Does utilization of screening mammography explain racial and ethnic differences in breast cancer? Ann Intern Med 144(8):541–553PubMed
4.
go back to reference Diaz LK et al (2007) Triple negative breast carcinoma and the basal phenotype: from expression profiling to clinical practice. Adv Anat Pathol 14(6):419–430PubMedCrossRef Diaz LK et al (2007) Triple negative breast carcinoma and the basal phenotype: from expression profiling to clinical practice. Adv Anat Pathol 14(6):419–430PubMedCrossRef
5.
go back to reference Carey LA et al (2006) Race, breast cancer subtypes, and survival in the carolina breast cancer study. JAMA 295(21):2492–2502PubMedCrossRef Carey LA et al (2006) Race, breast cancer subtypes, and survival in the carolina breast cancer study. JAMA 295(21):2492–2502PubMedCrossRef
6.
go back to reference Kim MJ et al (2006) Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol 37(9):1217–1226PubMedCrossRef Kim MJ et al (2006) Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol 37(9):1217–1226PubMedCrossRef
7.
go back to reference Rakha EA, Reis-Filho JS, Ellis IO (2008) Basal-like breast cancer: a critical review. J Clin Oncol 26(15):2568–2581PubMedCrossRef Rakha EA, Reis-Filho JS, Ellis IO (2008) Basal-like breast cancer: a critical review. J Clin Oncol 26(15):2568–2581PubMedCrossRef
8.
go back to reference Yang XR et al (2007) Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev 16(3):439–443PubMedCrossRef Yang XR et al (2007) Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev 16(3):439–443PubMedCrossRef
9.
go back to reference Livasy CA et al (2006) Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 19(2):264–271PubMedCrossRef Livasy CA et al (2006) Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 19(2):264–271PubMedCrossRef
10.
go back to reference Fulford LG et al (2006) Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast. Histopathology 49(1):22–34PubMedCrossRef Fulford LG et al (2006) Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast. Histopathology 49(1):22–34PubMedCrossRef
11.
go back to reference Ding L et al (2006) Identification of EZH2 as a molecular marker for a precancerous state in morphologically normal breast tissues. Cancer Res 66(8):4095–4099PubMedCrossRef Ding L et al (2006) Identification of EZH2 as a molecular marker for a precancerous state in morphologically normal breast tissues. Cancer Res 66(8):4095–4099PubMedCrossRef
12.
go back to reference Kleer CG et al (2003) EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA 100(20):11606–11611PubMedCrossRef Kleer CG et al (2003) EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA 100(20):11606–11611PubMedCrossRef
13.
go back to reference Alford SH et al (2012) Increased risk for distant metastasis in patients with familial early-stage breast cancer and high EZH2 expression. Breast Cancer Res Treat 132(2):429–437PubMedCrossRef Alford SH et al (2012) Increased risk for distant metastasis in patients with familial early-stage breast cancer and high EZH2 expression. Breast Cancer Res Treat 132(2):429–437PubMedCrossRef
14.
go back to reference Pietersen AM et al (2008) EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast cancer. Breast Cancer Res 10(6):R109PubMedCrossRef Pietersen AM et al (2008) EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast cancer. Breast Cancer Res 10(6):R109PubMedCrossRef
15.
go back to reference Bachmann IM et al (2006) EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol 24(2):268–273PubMedCrossRef Bachmann IM et al (2006) EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol 24(2):268–273PubMedCrossRef
16.
go back to reference Raaphorst FM et al (2003) Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene. Neoplasia 5(6):481–488PubMed Raaphorst FM et al (2003) Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene. Neoplasia 5(6):481–488PubMed
17.
go back to reference Gonzalez ME et al (2009) Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1. Oncogene 28(6):843–853PubMedCrossRef Gonzalez ME et al (2009) Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1. Oncogene 28(6):843–853PubMedCrossRef
18.
19.
go back to reference Stark A, Kleer CG, Martin I, Baffour A, Nsiah-Asare A, Takyi V, Braman M, Zarbo R, Wicha MS, Newman LA (2010) African ancestry and higher prevalence of triple negative breast cancer: findings from an international study. Cancer 116(21):4926–4932PubMedCrossRef Stark A, Kleer CG, Martin I, Baffour A, Nsiah-Asare A, Takyi V, Braman M, Zarbo R, Wicha MS, Newman LA (2010) African ancestry and higher prevalence of triple negative breast cancer: findings from an international study. Cancer 116(21):4926–4932PubMedCrossRef
20.
go back to reference Huo D et al (2009) Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer. J Clin Oncol 27(27):4515–4521PubMedCrossRef Huo D et al (2009) Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer. J Clin Oncol 27(27):4515–4521PubMedCrossRef
21.
go back to reference Gonzalez ME, DuPrie ML, Krueger H, Merajver SD, Ventura AC, Toy KA, Kleer CG (2011) Histone methyltransferase EZH2 induces Akt-dependent genomic instability and BRCA1 inhibition in breast cancer. Cancer Res 71(6):2360–2370PubMedCrossRef Gonzalez ME, DuPrie ML, Krueger H, Merajver SD, Ventura AC, Toy KA, Kleer CG (2011) Histone methyltransferase EZH2 induces Akt-dependent genomic instability and BRCA1 inhibition in breast cancer. Cancer Res 71(6):2360–2370PubMedCrossRef
22.
go back to reference Kunju LP et al (2011) EZH2 and ALDH-1 mark breast epithelium at risk for breast cancer development. Mod Pathol 24(6):786–793PubMedCrossRef Kunju LP et al (2011) EZH2 and ALDH-1 mark breast epithelium at risk for breast cancer development. Mod Pathol 24(6):786–793PubMedCrossRef
23.
go back to reference Newman LA et al (2006) Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status. J Clin Oncol 24(9):1342–1349PubMedCrossRef Newman LA et al (2006) Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status. J Clin Oncol 24(9):1342–1349PubMedCrossRef
24.
go back to reference Chlebowski RT et al (2005) Ethnicity and breast cancer: factors influencing differences in incidence and outcome. J Natl Cancer Inst 97(6):439–448PubMedCrossRef Chlebowski RT et al (2005) Ethnicity and breast cancer: factors influencing differences in incidence and outcome. J Natl Cancer Inst 97(6):439–448PubMedCrossRef
25.
go back to reference Nalwoga H et al (2007) Frequency of the basal-like phenotype in African breast cancer. APMIS 115(12):1391–1399PubMedCrossRef Nalwoga H et al (2007) Frequency of the basal-like phenotype in African breast cancer. APMIS 115(12):1391–1399PubMedCrossRef
26.
go back to reference Ijaduola TG, Smith EB (1998) Pattern of breast cancer among white-American, African-American, and nonimmigrant west-African women. J Natl Med Assoc 90(9):547–551PubMed Ijaduola TG, Smith EB (1998) Pattern of breast cancer among white-American, African-American, and nonimmigrant west-African women. J Natl Med Assoc 90(9):547–551PubMed
27.
go back to reference Awadelkarim KD et al (2011) Basal-like phenotype in a breast carcinoma case series from Sudan: prevalence and clinical/pathological correlations. Patholog Res Int 2011:806831PubMed Awadelkarim KD et al (2011) Basal-like phenotype in a breast carcinoma case series from Sudan: prevalence and clinical/pathological correlations. Patholog Res Int 2011:806831PubMed
28.
go back to reference Rosen PP (2008) Rosen’s breast pathology, in Rosen’s breast pathology. In: Rosen PP (ed) Lippincott Williams & Wilkins, Philadelphia Rosen PP (2008) Rosen’s breast pathology, in Rosen’s breast pathology. In: Rosen PP (ed) Lippincott Williams & Wilkins, Philadelphia
29.
go back to reference Collett K et al (2006) Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer. Clin Cancer Res 12(4):1168–1174PubMedCrossRef Collett K et al (2006) Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer. Clin Cancer Res 12(4):1168–1174PubMedCrossRef
30.
go back to reference Bracken AP et al (2003) EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J 22(20):5323–5335PubMedCrossRef Bracken AP et al (2003) EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J 22(20):5323–5335PubMedCrossRef
31.
go back to reference Gong Y et al (2011) Polycomb group protein EZH2 is frequently expressed in inflammatory breast cancer and is predictive of worse clinical outcome. Cancer 117(24):5476–5484PubMedCrossRef Gong Y et al (2011) Polycomb group protein EZH2 is frequently expressed in inflammatory breast cancer and is predictive of worse clinical outcome. Cancer 117(24):5476–5484PubMedCrossRef
32.
go back to reference Ding L, Kleer CG (2006) Enhancer of Zeste 2 as a marker of preneoplastic progression in the breast. Cancer Res 66(19):9352–9355PubMedCrossRef Ding L, Kleer CG (2006) Enhancer of Zeste 2 as a marker of preneoplastic progression in the breast. Cancer Res 66(19):9352–9355PubMedCrossRef
33.
go back to reference Chen H, Rossier C, Antonarakis SE (1996) Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2. Genomics 38(1):30–37PubMedCrossRef Chen H, Rossier C, Antonarakis SE (1996) Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2. Genomics 38(1):30–37PubMedCrossRef
34.
go back to reference Laible G et al (1997) Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres. EMBO J 16(11):3219–3232PubMedCrossRef Laible G et al (1997) Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres. EMBO J 16(11):3219–3232PubMedCrossRef
35.
go back to reference Sewalt RG et al (1998) Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes. Mol Cell Biol 18(6):3586–3595PubMed Sewalt RG et al (1998) Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes. Mol Cell Biol 18(6):3586–3595PubMed
36.
go back to reference Laible G et al (1999) The murine polycomb-group genes Ezh1 and Ezh2 map close to Hox gene clusters on mouse chromosomes 11 and 6. Mamm Genome 10(3):311–314PubMedCrossRef Laible G et al (1999) The murine polycomb-group genes Ezh1 and Ezh2 map close to Hox gene clusters on mouse chromosomes 11 and 6. Mamm Genome 10(3):311–314PubMedCrossRef
37.
go back to reference Varambally S et al (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419(6907):624–629PubMedCrossRef Varambally S et al (2002) The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419(6907):624–629PubMedCrossRef
38.
go back to reference Kuzmichev A et al (2004) Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3. Mol Cell 14(2):183–193PubMedCrossRef Kuzmichev A et al (2004) Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3. Mol Cell 14(2):183–193PubMedCrossRef
39.
go back to reference Su IH et al (2005) Polycomb group protein ezh2 controls actin polymerization and cell signaling. Cell 121(3):425–436PubMedCrossRef Su IH et al (2005) Polycomb group protein ezh2 controls actin polymerization and cell signaling. Cell 121(3):425–436PubMedCrossRef
40.
go back to reference van der Vlag J, Otte AP (1999) Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat Genet 23(4):474–478PubMedCrossRef van der Vlag J, Otte AP (1999) Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nat Genet 23(4):474–478PubMedCrossRef
41.
go back to reference Huang L, Pardee AB (2000) Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment. Mol Med 6(10):849–866PubMed Huang L, Pardee AB (2000) Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment. Mol Med 6(10):849–866PubMed
42.
go back to reference Miranda TB et al (2009) DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther 8(6):1579–1588PubMedCrossRef Miranda TB et al (2009) DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther 8(6):1579–1588PubMedCrossRef
43.
go back to reference Tan J et al (2007) Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev 21(9):1050–1063PubMedCrossRef Tan J et al (2007) Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev 21(9):1050–1063PubMedCrossRef
44.
go back to reference Puppe J et al (2009) BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to Polycomb Repressive Complex 2-inhibitor 3-deazaneplanocin A. Breast Cancer Res 11(4):R63PubMedCrossRef Puppe J et al (2009) BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to Polycomb Repressive Complex 2-inhibitor 3-deazaneplanocin A. Breast Cancer Res 11(4):R63PubMedCrossRef
Metadata
Title
Invasive breast carcinomas in Ghana: high frequency of high grade, basal-like histology and high EZH2 expression
Authors
Judy Pang
Kathy A. Toy
Ken A. Griffith
Baffour Awuah
Solomon Quayson
Lisa A. Newman
Celina G. Kleer
Publication date
01-08-2012
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-012-2055-z

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