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Open Access 01-12-2017 | Research article

Expression of enhancer of zeste homolog 2 correlates with survival outcome in patients with metastatic breast cancer: exploratory study using primary and paired metastatic lesions

Authors: Hitoshi Inari, Nobuyasu Suganuma, Kae Kawachi, Tatsuya Yoshida, Takashi Yamanaka, Yoshiyasu Nakamura, Mitsuyo Yoshihara, Hirotaka Nakayama, Ayumi Yamanaka, Katsuhiko Masudo, Takashi Oshima, Tomoyuki Yokose, Yasushi Rino, Satoru Shimizu, Yohei Miyagi, Munetaka Masuda

Published in: BMC Cancer | Issue 1/2017

Abstract

Background

In metastatic breast cancer, the status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as the Ki-67 index sometimes change between primary and metastatic lesions. However, the change in expression levels of enhancer of zeste homolog 2 (EZH2) between primary and metastatic lesions has not been determined in metastatic breast cancer.

Methods

Ninety-six metastatic breast cancer patients had biopsies or resections of metastatic lesions between September 1990 and February 2014 at the Kanagawa Cancer Center. We evaluated ER, PR, HER2, Ki-67, and EZH2 in primary lesions and their corresponding metastatic lesions using immunohistochemistry. We examined the change in expression of EZH2 between primary and metastatic lesions, the correlation between the expression of EZH2 and the expression of other biomarkers, and the relationship between EZH2 expression and patient outcome in metastatic breast cancer.

Results

EZH2 expression was significantly higher in metastatic lesions compared with primary lesions. EZH2 expression was highly correlated with Ki-67 expression in primary and metastatic lesions. High-level expression of EZH2 was associated with poorer disease-free survival (DFS) outcomes in patients with primary lesions (P < 0.001); however, high-level expression of EZH2 was not associated with poorer DFS outcomes in patients with metastatic lesions (P = 0.063). High-level expression of EZH2 was associated with poorer overall survival (OS) postoperatively in patients with primary (P = 0.001) or metastatic lesions (P = 0.005). High-level expression of EZH2 was associated with poorer OS outcomes after recurrence in patients with metastatic lesions (P = 0.014); however, high-level expression of EZH2 was not associated with poorer OS outcomes after recurrence in patients with primary lesions (P = 0.096). High-level expression of EZH2 in metastatic lesions was independently associated with poorer OS outcomes after recurrence.

Conclusions

EZH2 expression was significantly increased in metastatic lesions compared with primary lesions. High-level expression of EZH2 in metastatic lesions was associated with poorer OS outcomes after primary surgery and recurrence.

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Hitoshi I, Nobuyasu S, Kae K, Tatsuya Y, Hirotaka N, Takashi Y, et al. Correlation of expression of enhancer of zeste homolog 2 with the survival outcome in patients with metastatic breast cancer using primary and paired metastatic lesions. J Clin Oncol. 2016;34:e23227.

Title: Expression of enhancer of zeste homolog 2 correlates with survival outcome in patients with metastatic breast cancer: exploratory study using primary and paired metastatic lesions
Authors: Hitoshi Inari
Nobuyasu Suganuma
Kae Kawachi
Tatsuya Yoshida
Takashi Yamanaka
Yoshiyasu Nakamura
Mitsuyo Yoshihara
Hirotaka Nakayama
Ayumi Yamanaka
Katsuhiko Masudo
Takashi Oshima
Tomoyuki Yokose
Yasushi Rino
Satoru Shimizu
Yohei Miyagi
Munetaka Masuda
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-017-3154-3

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