Apoptosis as a possible candidate mechanism for removal of tamoxifen-related endometrial cells with KRAS mutations.
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.
Tsujioka
Hiroshi
H
Department of Obstetrics and Gynecology, Fukuoka University Faculty of Medicine, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. tsujioka@fukuoka-u.ac.jp
Hachisuga
Toru
T
Hikita
Shoko
S
Ueda
Taeko
T
Yotsumoto
Fusanori
F
Shirota
Kyoko
K
Yoshizato
Toshiyuki
T
Kawarabayashi
Tatsuhiko
T
Kuroki
Masahide
M
Miyamoto
Shingo
S
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
D018931:Antineoplastic Agents, Hormonal; D017931:DNA Primers; D013629:Tamoxifen