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

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

doi:10.1007/s10549-018-05092-w

I M Alhudiri, C C Nolan + Show 5 more

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https://doi.org/10.1007/s10549-018-05092-w

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Abstract

Lamins A/C, a major component of the nuclear lamina, play 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. 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. 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 < 0.001), larger tumour size (p = 0.004), poor Nottingham Prognostic Index score (p < 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). 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.

Highlights

IntroductionType V intermediate filament proteins, are the major component of the nuclear lamina [1] and are classified into A (lamin A and C) and B types
Lamins, type V intermediate filament proteins, are the major component of the nuclear lamina [1] and are classified into A and B types
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

Summary

Introduction

Type V intermediate filament proteins, are the major component of the nuclear lamina [1] and are classified into A (lamin A and C) and B types. Lamin A/C are implicated in a multitude of functions within the cell [2] including binding to chromatin, maintaining nuclear integrity, apoptosis and regulating gene expression and cell proliferation. Reduced or negative lamin A/C expression is associated with poor prognosis in a number of cancers including gastric carcinoma, lymphomas, lung, colon and breast cancer [23, 25,26,27,28,29]. Some studies of lamin A/C expression in breast cancer have reported decreased expression [24, 28,29,30,31] Most of these studies included small sample sizes and with scarce comment of the clinical outcome. To assess the prognostic effect of lamin A/C in breast cancer and association with different clinical parameters, we investigated its expression in a large and wellcharacterised series of early-stage breast carcinoma with a long-term follow-up and correlated this with clinicopathological variables and outcome

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