title: Prognostic significance of geminin expression levels in Ki67-high subset of estrogen receptor-positive and HER2-negative breast cancers.
abstract: BACKGROUND
  Indication for chemotherapy in estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancers is determined on the basis of Ki67 expression level. However, since Ki67-high cancers are not necessarily sensitive to chemotherapy, identification of such patients who do not need chemotherapy is an important issue.
  
  
  METHODS
  We used immunohistochemical staining to examine the expression levels of ER, progesterone receptor (PgR), Ki67, and geminin, a marker of S to G2/M phases, in 80 ER-positive/HER2-negative breast cancers. The labeling indices of Ki67 and geminin were determined and cutoff values were set at 15 and 6 %, respectively.
  
  
  RESULTS
  Ki67 and geminin expression levels were significantly associated with nuclear grade. In the Ki67-low subset, 26 out of 28 (92.9 %) cancers were geminin low and in the Ki67-high subset, 31 out of 52 (59.6 %) were geminin high. Distant disease-free survival (DDFS) of the geminin-high subset was significantly poorer than that of the geminin-low subset (P = 0.009). In the Ki67-low subset, only one patient showed recurrence. Metastasis was detected in eight out of 31 (25.8 %) patients in the geminin-high group of the Ki67-high subset, but no recurrence was observed in the geminin-low group of the Ki67-high subset.
  
  
  CONCLUSIONS
  Geminin-high breast cancers are significantly associated with worse prognosis. Since poorer prognosis was recognized only in the geminin-high group in Ki67-high cancers, we speculate that geminin may be useful for identifying patients in the Ki67-high subset who can avoid unnecessary chemotherapy.
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yagi
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Inoue
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Yanai
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Murase
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Miyagawa
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Enomoto
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Nishimukai
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takatsuka
authors.affiliation: Surgical Pathology, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.affiliation: Department of Medical Informatics, Niigata University Medical and Dental Hospital, Asahimachidori 1-754, Chuo-ku, Niigata, 951-8520, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Akazawa
authors.affiliation: Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan. ymiyoshi@hyo-med.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D064248:Geminin / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D064248:Geminin; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C577995:GMNN protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; Geminin; Ki67; Luminal subtype; Prognosis