The characteristics and prognostic significance of histone H1 expression in breast cancer

Lashen, Ayat G.; Almalki, Nabeelah; Toss, Michael; Mirza, Sameer; Malki, Mohammed Imad; Rutland, Catrin S.; Jeyapalan, Jennie N.; Green, Andrew R.; Mongan, Nigel P.; Madhusudan, Srinivasan; Rakha, Emad A.

Abstract

Histone H1 (H.H1) is involved in chromatin organisation and gene regulation and is overexpressed in many malignant tumours, including breast cancer (BC). This study proposed and evaluated the prognostic role of H.H1 expression in BC.

H.H1 mRNA expression was evaluated in publicly available BC dataset bc-GenExMiner database (n=4421). H.H1 protein expression was assessed immunohistochemically in a well-characterised early-stage BC cohort (n=1311), and associations with clinicopathological data and survival outcomes were evaluated.

At the mRNA level, there was a significant association between high H.H1 mRNA and basal-like BC subtype and with poor outcome. The association with shorter survival was observed in the whole cohort and in the basal-like class. H.H1 protein expression was detected in both tumour cells and surrounding stroma. Total expression was detected in 72% of the cases including 28% in tumour cell nuclei and 44% in the stroma. There was strong association between high tumour H.H1 expression and triple-negative BC (TNBC) subtype (p=0.007) and with shorter survival (p=0.019), independent of other variables including tumour size, histologic tumour grade, and lymph node status.

H.H1 expression is associated with poor prognosis in BC. Given poor prognostic role of H.H1 in TNBC, it may represent a potential therapeutic target for patients with this aggressive disease.

Citation

Lashen, A. G., Almalki, N., Toss, M., Mirza, S., Malki, M. I., Rutland, C. S., Jeyapalan, J. N., Green, A. R., Mongan, N. P., Madhusudan, S., & Rakha, E. A. (2024). The characteristics and prognostic significance of histone H1 expression in breast cancer. Pathology, 56(6), 826-833. https://doi.org/10.1016/j.pathol.2024.03.012

• Journal Article Type: Article
• Acceptance Date: Mar 27, 2024
• Online Publication Date: Jun 8, 2024
• Publication Date: 2024-10
• Deposit Date: Apr 12, 2024
• Publicly Available Date: Jun 9, 2025
• Journal: Pathology
• Print ISSN: 0031-3025
• Electronic ISSN: 1465-3931
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 56
• Issue: 6
• Pages: 826-833
• DOI: https://doi.org/10.1016/j.pathol.2024.03.012
• Keywords: Breast cancer; histone H1; endocrine; prognosis; molecular classes
• Public URL: https://nottingham-repository.worktribe.com/output/33565822
• Publisher URL: https://www.sciencedirect.com/science/article/abs/pii/S0031302524001430