ETS transcription factor ESE-1/Elf3 is an independent prognostic factor of survival in HR+HER2+ breast cancer patients

Abstract

Purpose

The ETS transcription factor ESE-1 has been shown to be important in HER2+ breast cancer and ESE-1 mRNA expression has been shown to associate with prognostic outcomes in the HER2+ subtype, as well as in ER+, HER2+ luminal B patients. However, the clinical significance of ESE-1 protein expression remains unknown. The purpose of the current exploratory study is to evaluate the prognostic value of ESE-1 protein expression in molecular breast cancer subtypes with special emphasis on hormone receptor positive HER2+(HR+ HER2+) and the HER2 positive (HER2+-only) breast cancer patients.

Methods

We developed a mouse monoclonal anti-ESE-1 antibody, verified its specificity, epitope, and used immunohistochemical staining to assess ESE-1 expression in an IBC approved archive of 957 breast tumor samples. Using Pearson product correlation, contingency analysis, and long rank P value testing, we analyzed the association of ESE-1 expression with clinicopathological features and survival outcomes in HR+HER2; HR+HER2+; HR HER2 (Triple negative) and HRHER2+ (HER2 subtype) patients.

Results

ESE-1, nuclear or cytoplasmic, was not significantly associated with survival outcomes in HR+HER2, triple-negative, or HER2+-only breast cancer patients. However, high nuclear ESE-1 was associated with poor survival outcomes in hormone receptor positive (ERα+, PR+) HER2+ patients and was an independent prognostic marker for that group.

Conclusions

This study provides evidence for prognostic significance of nuclear ESE-1 in ERalpha positive breast cancers patients also positive for HER2 indicating that crosstalk between ERalpha and ESE-1 in HER2+ tumors could be important for prognostic outcomes. Further studies regarding the nature of interaction between ESE-1 and ERalpha in these tumors are warranted.

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Abbreviations

ER:

Estrogen receptor

PgR:

Progesterone receptor

ErbB2:

Erb-b2 receptor tyrosine kinase 2/human epidermal growth factor receptor 2

AR:

Androgen receptor

Apop:

Apoptotic

Mit:

Mitotic

LN:

Lymph node

Elf3/ESE-1:

E74 like ETS transcription factor 3/Epithelial specific ETS transcription factor

TAD:

Transcription activation domain

AT-hook:

AT-hook DNA binding motif

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Acknowledgements

We thank Dr. Virginia Borges and Dr. Traci Lyons for reviewing the manuscript and for providing kind suggestions regarding interpretation of results. This work has been funded by Cancer league of Colorado grant

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Correspondence to Arthur Gutierrez-Hartmann.

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Authors report no competing financial interest in relation to the work described.

Ethical approval

This study was performed according to REMARK guidelines for tumor prognostic studies [20]. The patient samples used were originally covered by an approved IRB protocol from the Massachusetts General Hospital, Boston, MA.

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Informed consent was obtained from the participants included in the study.

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Kar, A., Koto, K., Walker, D. et al. ETS transcription factor ESE-1/Elf3 is an independent prognostic factor of survival in HR+HER2+ breast cancer patients. Breast Cancer Res Treat 182, 601–612 (2020). https://doi.org/10.1007/s10549-020-05734-y

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Keywords

  • ESE-1/ELF3
  • HER2+
  • Eralpha positive
  • Breast cancer
  • Prognostic