Division of Breast Surgery, The University of Nottingham, Nottingham, UK.
Genetic Engineering Department, Biotechnology Research Centre, Tripoli, Libya.
Breast Cancer Res Treat. 2019 Apr;174(3):661-668. doi: 10.1007/s10549-018-05092-w. Epub 2019 Jan 4.
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.
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。
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。
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)。
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。