Asch-Kendrick Rebecca J, Samols Mark A, Lilo Mohammed T, Subhawong Andrea P, Sharma Rajni, Illei Peter B, Argani Pedram, Cimino-Mathews Ashley
J Clin Pathol. 2014 Sep;67(9):768-71. doi: 10.1136/jclinpath-2014-202272.
NKX3.1 is an androgen-regulated tumour suppressor gene that is downregulated in prostate carcinoma. Immunohistochemistry for NKX3.1 is primarily specific for prostatic-derived tumours and tissue but is reported in a small number of breast carcinomas. NKX3.1 is also shown to inhibit estrogen receptor (ER) signalling in breast carcinoma models. Here, we investigate labelling of NKX3.1 in invasive ductal (IDC) and lobular (ILC) carcinomas of the breast with full characterisation of ER, progesterone receptor (PR), androgen receptor (AR) and Her2 status.
Tissue microarrays of 86 primary IDC and 37 ILC were labelled for NKX3.1. The IDC consisted of 20 luminal A, 7 luminal B, 14 Her2, and 45 triple negative carcinomas. The ILC consisted of 34 luminal A and 3 luminal B cases. NKX3.1 expression was scored as percentage nuclear labelling and labelling intensity.
Nuclear NKX3.1 labelling was seen in 2 IDC (2%) and 10 ILCs (27%). labelling intensity was weak in all cases (1–100% nuclear positivity). Positive NKX3.1 labelling was significantly associated with ILC (p<0.0001). NKX3.1 labelling was seen only in ER and AR-positive carcinomas, which showed a significant correlation (p=0.0003 and p=0.0079, respectively). Expression was not correlated with tumour stage, size, Her2 expression, presence of lymph node metastases or age.
This is the first study to evaluate NKX3.1 expression in breast carcinomas with known ER, PR, AR and Her2 status. Further studies are needed to evaluate what potential role NKX3.1 plays in ER and AR signalling and hormonal treatment response in breast carcinomas.
NKX3.1是一种雄激素调节的肿瘤抑制基因，在前列腺癌中表达下调。NKX3.1的免疫组织化学主要对前列腺来源的肿瘤和组织具有特异性，但在少数乳腺癌中也有报道。在乳腺癌模型中，NKX3.1也被证明可抑制雌激素受体（ER）信号传导。在此，我们研究NKX3.1在乳腺浸润性导管癌（IDC）和小叶癌（ILC）中的标记情况，并全面分析ER、孕激素受体（PR）、雄激素受体（AR）和Her2状态。
对86例原发性IDC和37例ILC的组织芯片进行NKX3.1标记。IDC包括20例腔面A型、7例腔面B型、14例Her2型和45例三阴性癌。ILC包括34例腔面A型和3例腔面B型病例。NKX3.1表达按核标记百分比和标记强度评分。
在2例IDC（2%）和10例ILC（27%）中可见核NKX3.1标记。所有病例的标记强度均较弱（核阳性率为1–100%）。NKX3.1阳性标记与ILC显著相关（p<0.0001）。仅在ER和AR阳性的癌中可见NKX3.1标记，二者显示出显著相关性（分别为p=0.0003和p=0.0079）。表达与肿瘤分期、大小、Her2表达、淋巴结转移情况或年龄无关。
这是第一项评估已知ER、PR、AR和Her2状态的乳腺癌中NKX3.1表达的研究。需要进一步研究来评估NKX3.1在乳腺癌的ER和AR信号传导以及激素治疗反应中发挥的潜在作用。
