Effect of the normal mammary differentiation regulator ELF5 upon clinical outcomes of triple negative breast cancers patients
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Elf5 is a transcription factor previously shown to be involved in regulating cell differentiation in both normal and pathological breast tissues. Pertinently, Elf5 was reported to interact with the FOXA1 transcription factor, a pivotal regulatory factor in a subset of AR overexpressing triple negative cancer (TNBC) cases.
We examined the correlation among AR, FOXA1, and Elf5 expression in a series of TNBC cases. The cases were retrieved from surgical pathological files of Tohoku University Hospital Japan and consisted of 60 cases operated between the year 1999 and 2007. An additional cohort cases of 51 TNBC ductal carcinoma in situ was used to compare invasive and non-invasive TNBC.
In our cohort, 47% of all carcinomas were positive for Elf5, with a significantly higher proportion of Elf5 positive cases occurring in the younger age groups (p = 0.0061). Elf5 immunoreactivity was not associated with any other clinicopathological factors examined in this study. However, Elf5 expression was associated with decreased overall and disease-free survival of the patients (Peto–Peto modification of Gehan–Wilcoxon test, OS p = 0.132, DFS p = 0.1 (LI cutoff 10%); OS p = 0.038, DFS p = 0.021 (LI cutoff 50%)). Of particular interest, its effects on survival were more pronounced in the EGFR−/CK5/6− (non-basal surrogate) than the EGFR+ and/or CK5/6+ (basal-surrogate) subtype of TNBC.
Elf5 is present in TNBC and its status was significantly correlated with overall survival of the patients. Further studies examining possible interactions between Elf5 and other factors in TNBC could contribute to disentangling TNBC biology.
KeywordsElf5 Breast cancer TNBC Steroids Basal EGFR Differentiation Androgens Estrogens Survival outcomes
We would like to thank staff and colleagues at the Department of Anatomical Pathology for their guidance and support during manuscript preparation. We would also like to thank Dr Vladimiros Thoma for his careful proofreading of the manuscript.
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Conflict of interest
The authors have no relevant conflicts of interest.