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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2016

Open Access 01-12-2016 | Research

EZH2 overexpression in different immunophenotypes of breast carcinoma and association with clinicopathologic features

Authors: Shuangping Guo, Xia Li, Joseph Rohr, Yingmei Wang, Shirong Ma, Peng Chen, Zhe Wang

Published in: Diagnostic Pathology | Issue 1/2016

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Abstract

Background

Enhancer of zest homolog 2 (EZH2), a histone 3 methyltransferase, is associated with aggressive behavior of many tumors and is a promising target of molecular therapy.

Methods

To better elucidate the relevance of EZH2 in breast cancer subtypes, we evaluated EZH2 expression in 226 invasive breast carcinomas with four distinct immunophenotypes and in association with clinicopathological features.

Results

Of these cases, 138 (61.1 %) were defined as EZH2-overexpressing with a multiplicative score > 3. EZH2 expression was inversely related to the status of ER and PR (Chi-square, p < 0.001), and it was significantly associated with HER2 positivity, high proliferative index, and high histologic grade (Chi-square, p < 0.05). ER-positive breast carcinoma with low proliferative index (Ki67 < 14 %) showed the lowest expression and triple-negative breast carcinoma showed the highest overexpression of EZH2, 18.5 % (10/54) versus 90.9 % (50/55) (Chi-square, p < 0.001). Intriguingly, 88 % (44/50) cases of grade 3 triple-negative breast carcinoma showed uniformly strong EZH2 expression with a multiplicative score of 9. The percentage of EZH2 overexpression in ER-positive breast carcinoma with a high proliferative index or HER2-positive cases were 61.2 and 74 %, respectively. Furthermore, EZH2 expression was significantly elevated in high-grade DCIS compared to benign lesions (90 % versus 0, p < 0.001). However, there is no association between EZH2 expression and the status of histone 3 lysine 27 trimethylation or other clinicopathologic features.

Conclusion

In summary, triple-negative breast carcinoma showed the highest overexpression of EZH2. EZH2 overexpression is associated aggressive pathologic features including high nuclear grade, high proliferative index, and positivity of HER2 of breast carcinoma.
Literature
1.
Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784–95.CrossRefPubMedPubMedCentral
2.
Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med. 2014;138(2):241–56.CrossRefPubMedPubMedCentral
3.
Rakha EA, Ellis IO. Triple-negative/basal-like breast cancer: review. Pathology. 2009;41(1):40–7.CrossRefPubMed
4.
Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109:25–32.CrossRefPubMed
5.
Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34.CrossRefPubMed
6.
Wang Y, Cao S, Chen Y. Molecular treatment of different breast cancers. Anticancer Agents Med Chem. 2015;15(6):701–20.CrossRefPubMed
7.
8.
Reijm EA, Timmermans AM, Look MP, et al. High protein expression of EZH2 is related to unfavorable outcome to tamoxifen in metastatic breast cancer. Ann Oncol. 2014;25(11):2185–90.CrossRefPubMed
9.
Bachmann IM, Halvorsen OJ, Collett K, et al. 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. 2006;24:268–73.CrossRefPubMed
10.
Karsli-Ceppioglu S, Dagdemir A, Judes G, et al. Epigenetic mechanisms of breast cancer: an update of the current knowledge. Epigenomics. 2014;6(6):651–64.CrossRefPubMed
11.
Gonzalez ME, Moore HM, Li X, et al. EZH2 expands breast stem cells through activation of NOTCH1 signaling. Proc Natl Acad Sci USA. 2014;111(8):3098–103.CrossRefPubMedPubMedCentral
12.
Li T, Cai J, Ding H, et al. EZH2participates in malignant biological behavior of epithelial ovarian cancer through regulating the expression of BRCA1. Cancer Biol Ther. 2014;15(3):271–8.CrossRefPubMedPubMedCentral
13.
14.
Granit RZ, Gabai Y, Hadar T, et al. EZH2 promotes a bi-lineage identity in basal-like breast cancercells. Oncogene. 2013;32(33):3886–95.CrossRefPubMed
15.
Holm K, Grabau D, Lövgren K, et al. Global H3K27 trimethylation and EZH2 abundance in breast tumor subtypes. Mol Oncol. 2012;6(5):494–506.CrossRefPubMed
16.
De Brot M, Rocha RM, Soares FA, et al. Prognostic impact of the cancer stem cell related markers ALDH1 and EZH2 in triple negative and basal-like breast cancers. Pathology. 2012;44(4):303–12.CrossRefPubMed
17.
Ren G, Baritaki S, Marathe H, et al. Polycomb protein EZH2 regulates tumor invasion via the transcriptional repression of the metastasis suppressor RKIP inbreast and prostate cancer. Cancer Res. 2012;72(12):3091–104.CrossRefPubMed
18.
Hussein YR, Sood AK, Bandyopadhyay S, et al. Clinical and biological relevance of enhancer of zeste homolog 2 in triple-negative breast cancer. Hum Pathol. 2012;43(10):1638–44.CrossRefPubMedPubMedCentral
19.
Kalashnikova EV, Revenko AS, Gemo AT, et al. ANCCA/ATAD2 overexpression identifies breast cancer patients with poor prognosis, acting to drive proliferation and survival of triple-negative cells through control of B-Myb and EZH2. Cancer Res. 2010;70(22):9402–12.CrossRefPubMedPubMedCentral
20.
Fujii S, Tokita K, Wada N, et al. MEK-ERK pathway regulates EZH2 overexpression in association with aggressive breast cancer subtypes. Oncogene. 2011;30(39):4118–28.CrossRefPubMed
21.
Collett K, Eide GE, Arnes J, et al. 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. 2006;12(4):1168–74.CrossRefPubMed
22.
Kleer CG, Cao Q, Varambally S, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A. 2003;100(20):11606–11.CrossRefPubMedPubMedCentral
23.
Bracken AP, Pasini D, Capra M, et al. EZH2 is downstream of the pRB-E2F pathway, essential for proliferationand amplified in cancer. EMBO J. 2003;22:5323–35.CrossRefPubMedPubMedCentral
24.
25.
Khaled WT, Choon Lee S, Stingl J, et al. BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells. Nat Commun. 2015;6:5987.CrossRefPubMedPubMedCentral
26.
Ding L, Erdmann C, Chinnaiyan AM, et al. Identification of EZH2 as a molecular marker for a precancerous state in morphologically normal breast tissues. Cancer Res. 2006;66(8):4095–9.CrossRefPubMed
27.
Ding L, Kleer CG. Enhancer of Zeste 2 as a marker of preneoplastic progression in the breast. Cancer Res. 2006;66(19):9352–5.CrossRefPubMed
28.
Gonzalez ME, Li X, Toy K, et al. Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1. Oncogene. 2009;28(6):843–53.CrossRefPubMedPubMedCentral
Metadata
Title
EZH2 overexpression in different immunophenotypes of breast carcinoma and association with clinicopathologic features
Authors
Shuangping Guo
Xia Li
Joseph Rohr
Yingmei Wang
Shirong Ma
Peng Chen
Zhe Wang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2016
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-016-0491-5

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