J Korean Med Sci.  2019 Dec;34(49):e312. 10.3346/jkms.2019.34.e312.

Amplification of Stem Genes: New Potential Metastatic Makers in Patients with an Early Form of Breast Cancer

• Tsyganov M
• Ibragimova MK
• Pevzner AM
• Doroshenko AV
• Slonimskaya EM
• Litviakov

• KMID: 2466006
• DOI: http://doi.org/10.3346/jkms.2019.34.e312

Abstract

BACKGROUND
According to our previous studies, the presence of amplifications of stem genes can lead to their ectopic expression and this is associated with an increased activity of tumor stem cells in these patients. This leads to a high aggressiveness of the tumor and the development of metastatic disease. The aim was to evaluate the prognostic significance of the presence of amplifications of stem genes and their expression in patients with early breast cancer (BC).
METHODS
The study included 28 patients with T₁N(x)M₀ BC. We used surgical specimens, including formalin-fixed paraffin-embedded archive materials, for 8 patients. A microarray analysis was performed on high-density DNA chips from CytoScanHDArray to assess the status of copy number aberration (CNA) of stem genes locus. Gene expression was assessed using RT-qPCR.
RESULTS
CNA analysis of the studied tumors of patients without chemotherapy showed that 17/18 patients without metastases did not have two or more amplifications of chromosomal regions. Ten patients had visceral metastases. In 9/10 of these patients in the primary tumor there were two or more amplifications of the stem genes locus. Two or more amplifications of stem genes locus were found in 12 patients with stage I. Hematogenous metastases did not develop in all patients. Comparison of metastasis-free survival rates in groups of patients with 1 or without amplifications and with two or more amplifications showed statistically significant differences (P = 0.01).
CONCLUSION
Our studies have shown that the presence of clones with two or more amplifications of stem gene in patients with BC T₁N(x)M₀ has a significant prognostic value and determines an unfavorable prognosis for distant metastasis.

Keyword

Early Breast Cancer; Stem Genes; Amplification; Prognosis

MeSH Terms

Archives
Breast Neoplasms*
Breast*
Clone Cells
Drug Therapy
Ectopic Gene Expression
Gene Expression
Humans
Microarray Analysis
Neoplasm Metastasis
Neoplastic Stem Cells
Oligonucleotide Array Sequence Analysis
Prognosis
Survival Rate