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. Patients and 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). Conclusion: Apoptosis may play an important role in removing TAM treatment-related endometrial cells with KRAS mutations.