The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ

Al-Kawaz, Abdulbaqi; Miligy, Islam M.; Toss, Michael S.; Mohammed, Omar J.; Green, Andrew R.; Madhusudan, Srinivasan; Rakha, Emad A.

Abstract

Background
Impaired DNA repair mechanism is one of the cancer hallmarks. Flap Endonuclease 1 (FEN1) is essential for genomic integrity. FEN1 has key roles during base excision repair (BER) and replication. We hypothesised a role for FEN1 in breast cancer pathogenesis. This study aims to assess the role of FEN1 in breast ductal carcinoma in situ (DCIS).

Methods
Expression of FEN1 protein was evaluated in a large (n = 1015) well-characterised cohort of DCIS, comprising pure (n = 776) and mixed (DCIS coexists with invasive breast cancer (IBC); n = 239) using immunohistochemistry (IHC).

Results
FEN1 high expression in DCIS was associated with aggressive and high-risk features including higher nuclear grade, larger tumour size, comedo type necrosis, hormonal receptors negativity, higher proliferation index and triple-negative phenotype. DCIS coexisting with invasive BC showed higher FEN1 nuclear expression compared to normal breast tissue and pure DCIS but revealed significantly lower expression when compared to the invasive component. However, FEN1 protein expression in DCIS was not an independent predictor of local recurrence-free interval.

Conclusion
High FEN1 expression is linked to features of aggressive tumour behaviour and may play a role in the direct progression of DCIS to invasive disease. Further studies are warranted to evaluate its mechanistic roles in DCIS progression and prognosis.

Citation

Al-Kawaz, A., Miligy, I. M., Toss, M. S., Mohammed, O. J., Green, A. R., Madhusudan, S., & Rakha, E. A. (2021). The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ. Breast Cancer Research and Treatment, 188(1), 53-63. https://doi.org/10.1007/s10549-021-06271-y

• Journal Article Type: Article
• Acceptance Date: May 24, 2021
• Online Publication Date: Jun 12, 2021
• Publication Date: 2021-07
• Deposit Date: Jun 22, 2021
• Publicly Available Date: Jun 25, 2021
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Peer Reviewed: Peer Reviewed
• Volume: 188
• Issue: 1
• Pages: 53-63
• DOI: https://doi.org/10.1007/s10549-021-06271-y
• Keywords: Flap Endonuclease 1 (FEN1); Ductal Carcinoma in situ; Prognosis; Breast Cancer 2
• Public URL: https://nottingham-repository.worktribe.com/output/5719067
• Publisher URL: https://link.springer.com/article/10.1007/s10549-021-06271-y