Syed Binafsha Manzoor, Green Andrew R, Morgan David A L, Ellis Ian O, Cheung Kwok-Leung
Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, DE22 3DT Nottingham, United Kingdom.
Medical Research Centre, Liaquat University of Medical & Health Sciences, Jamshoro 71000, Pakistan.
Cancers (Basel). 2019 Jan 28;11(2):149. doi: 10.3390/cancers11020149.
: The role of liver kinase B1 (LKB1), a serine/threonine kinase, has been described in the development of PeutzJagher's syndrome, where a proportion (~45%) of patients have developed breast cancer in their lifetime. Cell line studies have linked LKB1 with oestrogen receptors (ER) and with the Adenosine monophosphate-activated protein kinase (AMPK) pathway for energy metabolism. However, limited studies have investigated protein expression of LKB1 in tumour tissues and its intracellular relationships. This study aimed to investigate the intracellular molecular relationships of LKB1 in older women with early operable primary breast cancer and its correlation with long-term clinical outcome. : Between 1973 and 2010, a consecutive series of 1758 older (≥70 years) women with T0-2N0-1M0 breast carcinoma were managed in a dedicated facility. Of these, 813 patients underwent primary surgery, and 575 had good quality tumour samples available for tissue microarray construction. LKB1 was assessed in 407 cases by indirect immunohistochemistry (IHC). Tumours with 30% or more of cells with cytoplasmic LKB1 expression were considered positive. LKB1 expression was compared with tumour size, histological grade, axillary lymph node stage, ER, PgR, EGFR, HER2, HER3, HER4, BRCA1&2, p53, Ki67, Bcl2, Muc1, E-Cadherin, CD44, basal (CK5, CK5/6, CK14 and CK17) and luminal (CK7/8, CK18 and CK19) cytokeratins, MDM2 and MDM4, and correlated with long-term clinical outcome. : Positive LKB1 expression was seen in 318 (78.1%) patients, and was significantly associated with high tumour grade, high Ki67, over-expression of HER2, VEGF, HER4, BRCA2, MDM2 and negative expression of CD44 (p < 0.05). There was no significant correlation with tumour size, axillary lymph node status, ER, PgR, p53, basal or luminal cytokeratins, Bcl2, Muc1, EGFR, HER3, MDM4, E-cadherin and BRCA1. LKB1 did not show any significant influence on survival in the overall population; however, in those patients receiving adjuvant endocrine therapy for ER positive tumours, those with positive LKB1 had significantly better 5-year breast cancer specific survival when compared to those without such expression (93% versus 74%, = 0.03). : LKB1 expression has shown association with poor prognostic factors in older women with breast cancer. However, LKB1 expression appears to be associated with better survival outcome among those patients receiving adjuvant endocrine therapy. Further research is required to explore its potential role as a therapeutic target.
丝氨酸/苏氨酸激酶肝激酶B1（LKB1）在黑斑息肉综合征的发生发展中发挥了作用，该综合征患者中有一定比例（约45%）在一生中会罹患乳腺癌。细胞系研究已将LKB1与雌激素受体（ER）以及能量代谢的腺苷单磷酸激活蛋白激酶（AMPK）途径联系起来。然而，对LKB1在肿瘤组织中的蛋白表达及其细胞内关系的研究有限。本研究旨在探讨LKB1在可早期手术的老年原发性乳腺癌女性患者中的细胞内分子关系及其与长期临床结局的相关性。1973年至2010年期间，在一个专门机构对连续的1758例年龄较大（≥70岁）的T0 - 2N0 - 1M0乳腺癌女性患者进行了管理。其中，813例患者接受了初次手术，575例有质量良好的肿瘤样本可用于构建组织芯片。通过间接免疫组织化学（IHC）对407例病例中的LKB1进行了评估。细胞质LKB1表达的细胞占30%或更多的肿瘤被视为阳性。将LKB1表达与肿瘤大小、组织学分级、腋窝淋巴结分期、ER、PgR、EGFR、HER2、HER3、HER4、BRCA1和2、p53、Ki67、Bcl2、Muc1、E - 钙黏蛋白、CD44、基底（CK5、CK5/6、CK14和CK17）和腔面（CK7/8、CK18和CK19）细胞角蛋白、MDM2和MDM4进行比较，并与长期临床结局相关联。318例（78.1%）患者LKB1表达呈阳性，且与高肿瘤分级、高Ki67、HER2、VEGF、HER4、BRCA2、MDM2过表达以及CD44阴性表达显著相关（p < 0.05）。与肿瘤大小、腋窝淋巴结状态、ER、PgR、p53、基底或腔面细胞角蛋白、Bcl2、Muc1、EGFR、HER3、MDM4、E - 钙黏蛋白和BRCA1无显著相关性。LKB1对总体人群的生存没有显著影响；然而，在那些接受ER阳性肿瘤辅助内分泌治疗的患者中，LKB1阳性患者的5年乳腺癌特异性生存率明显高于无此表达的患者（93%对74%，p = 0.03）。LKB1表达与老年乳腺癌女性患者的不良预后因素相关。然而，LKB1表达似乎与接受辅助内分泌治疗的患者更好的生存结局相关。需要进一步研究以探索其作为治疗靶点的潜在作用。
