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


CONCLUSIONS
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.
Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China.
Shuangping
S
Guo
Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China.
Xia
X
Li
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68105, NE, USA.
Joseph
J
Rohr
Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China.
Yingmei
Y
Wang
Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China.
Shirong
S
Ma
Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China.
Peng
P
Chen
Department of Pathology, Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi Province, 710032, China. zhwang@fmmu.edu.cn.
Zhe
Z
Wang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D010641:Phenotype; D063151:Polycomb Repressive Complex 2 / Q000032:analysis*; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D019394:Ki-67 Antigen; D063151:Polycomb Repressive Complex 2; D018719:Erb-b2 Receptor Tyrosine Kinases; C498409:EZH2 protein, human; C508053:ERBB2 protein, human
EZH2 overexpression; High nuclear grade; Immunophenotype; Proliferative index; Triple-negative breast carcinoma