title: NKX3.1 is expressed in ER-positive and AR-positive primary breast carcinomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Asch-Kendrick
authors.forename: Mark A
authors.initials: MA
authors.lastname: Samols
authors.forename: Mohammed T
authors.initials: MT
authors.lastname: Lilo
authors.forename: Andrea P
authors.initials: AP
authors.lastname: Subhawong
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Peter B
authors.initials: PB
authors.lastname: Illei
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Ashley
authors.initials: A
authors.lastname: Cimino-Mathews
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000556:secondary; D018275:Carcinoma, Lobular / Q000737:chemistry* / Q000556:secondary; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011944:Receptors, Androgen / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis*; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; C410798:AR protein, human; C491178:NKX3-1 protein, human; C508053:ERBB2 protein, human