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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan. inari-hitoshi@nifty.com.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Inari
authors.affiliation: Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Suganuma
authors.affiliation: Department of Pathology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan.
authors.forename: Kae
authors.initials: K
authors.lastname: Kawachi
authors.affiliation: Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Yoshihara
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yamanaka
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Masudo
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Department of Pathology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Rino
authors.affiliation: Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan. miyagi@gancen.asahi.yokohama.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. mmasuda@yokohama-cu.ac.jp.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
mesh_terms: D000328:Adult; D001706:Biopsy; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D019394:Ki-67 Antigen; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: EZH2; Epigenetics; Immunohistochemistry; Ki-67; Metastatic breast cancer; Prognostic factor