Bmi-1, c-myc, and Snail expression in primary breast cancers and their metastases--elevated Bmi-1 expression in late breast cancer relapses.

Breast cancer is known for its propensity to recur decades after treatment. The biology behind the phenomenon of tumor dormancy is still poorly understood. Bmi-1, c-myc, and Snail are transcription factors that have prognostic roles in several malignancies. In order to reveal whether any of these markers has impact on late relapses, we used immunohistochemistry to study the expression of Bmi-1, c-myc, Snail, and estrogen receptor in 73 primary breast cancers and in their metastatic relapses detected within 2 years, or 5 or 10 years after primary surgery. The expression of Bmi-1 was higher in the metastases than in their corresponding primary tumors in both early and late relapses. The highest expression of Bmi-1 was seen in the very late relapsing tumors (first tumor relapse after 10 years). Previously, Bmi-1 has been reported to function as a marker of tumor stem cells in breast cancer. Our results indicate that metastases, when compared to primary tumors, arise from tumor cells that have retained stem cell properties. We also analyzed the relationship between the expression of these markers and clinical parameters. A significant association between the expression of Bmi-1 and estrogen receptor was found. Nuclear expression of c-myc in primary tumors correlated with an increased risk for axillary lymph node metastasis.