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早期乳腺癌中核纤层蛋白 A/C 的表达及其预后价值。

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

机构信息

Division of Breast Surgery, The University of Nottingham, Nottingham, UK.

Genetic Engineering Department, Biotechnology Research Centre, Tripoli, Libya.

出版信息

Breast Cancer Res Treat. 2019 Apr;174(3):661-668. doi: 10.1007/s10549-018-05092-w. Epub 2019 Jan 4.

DOI:10.1007/s10549-018-05092-w
PMID:30610489
Abstract

PURPOSE

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.

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 < 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).

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.

摘要

目的

核层粘连蛋白 A/C 是核层的主要成分,在维持核完整性、基因表达调控、细胞增殖和凋亡中发挥关键作用。已有报道称,癌症中核层粘连蛋白 A/C 的表达减少是预后不良的标志。然而,其在乳腺癌中的临床意义仍有待确定。本研究旨在评估核层粘连蛋白 A/C 在早期乳腺癌中的表达及其预后意义。

方法

采用组织微阵列免疫组织化学染色,对诺丁汉原发性乳腺癌系列中获得的 938 例早期可手术乳腺癌的大型特征良好的系列进行核层粘连蛋白 A/C 的表达评估。评估核层粘连蛋白 A/C 表达与临床病理参数和结局的相关性。

结果

乳腺癌中核层粘连蛋白 A/C 的阳性表达率为 42.2%(n=398)。核层粘连蛋白 A/C 表达减少/缺失与高组织学分级(p<0.001)、更大的肿瘤大小(p=0.004)、较差的诺丁汉预后指数评分(p<0.001)、脉管侵犯(p=0.014)和远处转移的发展(p=0.027)显著相关。生存分析表明,核层粘连蛋白 A/C 表达减少/缺失与乳腺癌特异性生存时间缩短显著相关(p=0.008)。

结论

本研究表明核层粘连蛋白 A/C 在乳腺癌中发挥作用,其表达缺失与预后不良的变量和较短的结局相关。

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