title: High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival.
abstract: ATP-binding cassette (ABC) transporters are membrane proteins that efflux various compounds from cells, including chemotherapeutic agents, and are known to affect multidrug resistance. Recent reports disagree on whether ABCC11 is a risk factor for breast tumorigenesis, but its expression in breast cancer is poorly investigated. We hypothesized that both frequency and expression levels of ABC transporters in breast tumors would vary by cancer subtype, and be associated with prognosis. Here, we constructed a tissue microarray breast tumor samples from 281 patients, and analyzed expressions of ABCB1, ABCC1, ABCC11, and ABCG2 immunohistochemically. Breast cancer subtypes were determined by immunohistochemistry of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Protein expression was correlated to clinicopathological characteristics, clinical follow-up, and pathological complete response to neoadjuvant chemotherapy. The tissue microarray comprised 191 luminal A (68.0 %), 17 luminal B (6.0 %), 27 HER2 (9.6 %), and 46 triple-negative (16.4 %) samples. ABCC1 and ABCC11 expressions were associated with significantly shorter disease-free survival (P = 0.027 and P = 0.003, respectively). ABCC1, ABCC11, and ABCG2, but not ABCB1, were expressed significantly more, and more frequently, in aggressive subtypes. Patients with HER2+ and triple-negative tumor subtypes that expressed high levels of ABCC11 had significantly worse disease-free survival (P = 0.017 and P < 0.001, respectively). We have shown, for the first time, that ABCC1, ABCC11, and ABCG2 are highly expressed in aggressive breast cancer subtypes, and that tumor ABCC11 expression is associated with poor prognosis.
authors.affiliation: Department of Clinical Oncology and Breast Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan.
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ota
authors.forename: Mariko
authors.initials: M
authors.lastname: Kimura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shimizu
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tanabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Chishima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Koh-ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Takabe
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C435500:ABCC11 protein, human; C421109:multidrug resistance-associated protein 1