Expression of Lamin A/C in early-stage breast cancer and its prognostic value

Alhudiri, I.M.; Nolan, C.C.; Ellis, I.O.; Elzagheid, A.; Rakha, E.A.; Green, A.R.; Chapman, C.J.

Abstract

Purpose: Lamins A/C, a major component of the nuclear lamina, plays key roles in maintaining nuclear integrity, regulation of gene expression, cell proliferation and apoptosis. Reduced lamin A/C expression in cancer has been reported to be a sign of poor prognosis. However, its clinical significance in breast cancer remains to be defined. This study aimed to evaluate expression and prognostic significance of lamin A/C in early-stage breast cancer.

Methods: Using immunohistochemical staining of tissue microarrays, expression of lamin A/C was evaluated in a large well-characterised series of early-stage operable breast cancer (n=938) obtained from Nottingham Primary Breast Carcinoma Series. Association of lamin A/C expression with clinicopathological parameters and outcome was evaluated.

Results: Positive expression rate of lamin A/C in breast cancer was 42.2% (n=398). Reduced/loss of expression of lamin A/C was significantly associated with high histological grade (p [less than] 0.001), larger tumour size (p=0.004), poor Nottingham Prognostic Index (NPI) score (p [less than] 0.001), lymphovascular invasion (p=0.014) and development of distant metastasis (p=0.027). Survival analysis showed that reduced/loss of expression of lamin A/C was significantly associated with shorter breast cancer specific survival (p=0.008).

Conclusion: This study suggests lamin A/C plays a role in breast cancer and loss of its expression is associated with variables of poor prognosis and shorter outcome.

Citation

Alhudiri, I., Nolan, C., Ellis, I., Elzagheid, A., Rakha, E., Green, A., & Chapman, C. (2019). Expression of Lamin A/C in early-stage breast cancer and its prognostic value. Breast Cancer Research and Treatment, 174(3), 661–668. https://doi.org/10.1007/s10549-018-05092-w

• Journal Article Type: Article
• Acceptance Date: Dec 5, 2018
• Online Publication Date: Jan 4, 2019
• Publication Date: 2019-04
• Deposit Date: Dec 6, 2018
• Publicly Available Date: Jan 5, 2020
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 174
• Issue: 3
• Pages: 661–668
• DOI: https://doi.org/10.1007/s10549-018-05092-w
• Keywords: Breast cancer; Lamin A/C; Immunohistochemistry; Tissue microarray; Prognosis
• Public URL: https://nottingham-repository.worktribe.com/output/1380044
• Publisher URL: https://link.springer.com/article/10.1007%2Fs10549-018-05092-w
• Additional Information: Received: 5 December 2018; Accepted: 7 December 2018; First Online: 4 January 2019; : ; : Authors declare that they have no conflict of interests.; : All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Nottingham Research Ethics Committee 2 under the title “Development of a molecular genetic classification of breast cancer”.; : Informed consent was obtained from all individual participants included in the study.