title: Apoptosis as a possible candidate mechanism for removal of tamoxifen-related endometrial cells with KRAS mutations.
abstract: BACKGROUND
  Endometrial cell KRAS mutations are frequent in tamoxifen (TAM)-treated breast cancer patients. We previously demonstrated that most KRAS mutations disappeared after TAM cessation, suggesting the existence of a removal mechanism for endometrial cells with KRAS mutation. Here, the role of apoptosis in this mechanism was investigated.
  
  
  METHODS
  DNA was extracted from frozen endometrial polyps of 31 TAM-treated breast cancer patients. Codon 12 mutations in KRAS were detected by enriched polymerase chain reaction enzyme-linked minisequence assay. Apoptosis was detected by the TdT-mediated dUTP-biotin nick end-labeling (TUNEL) method and Ki-67 expression by immunohistochemistry. Relationships between KRAS mutations, the apoptosis index, and the Ki-67 index were determined.
  
  
  RESULTS
  KRAS mutations were observed in 9 of these patients. There was no significant relationship between the Ki-67 index and KRAS mutation. However, the apoptosis index was significantly higher in polyps with KRAS mutation (p=0.002).
  
  
  CONCLUSIONS
  Apoptosis may play an important role in removing TAM treatment-related endometrial cells with KRAS mutations.
authors.affiliation: Department of Obstetrics and Gynecology, Fukuoka University Faculty of Medicine, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. tsujioka@fukuoka-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsujioka
authors.forename: Toru
authors.initials: T
authors.lastname: Hachisuga
authors.forename: Shoko
authors.initials: S
authors.lastname: Hikita
authors.forename: Taeko
authors.initials: T
authors.lastname: Ueda
authors.forename: Fusanori
authors.initials: F
authors.lastname: Yotsumoto
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shirota
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoshizato
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D017931:DNA Primers; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D005260:Female; D011905:Genes, ras; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017931:DNA Primers; D013629:Tamoxifen