The NKX3.1 gene is an androgen-regulated homeodomain gene located on chromosome 8p21.2, whose expression is predominantly localized to prostate epithelium. The NKX3.1 protein acts as a nuclear transcription factor that has a critical function in prostate development and tumour suppression, and is a negative regulator of epithelial cell growth in prostate tissue. Apart from prostate epithelium, NKX3.1 is found in testis, ureter, and pulmonary bronchial mucous glands.
+ The proportion of prostate adenocarcinomas being NKX3.1 positive in the literature is highly varying but with the newest antibodies and a sensitive visualization system more than 90% are positive.
-/+ NKX3.1 is found in a minority (~20%) of prostatic small cell carcinomas and breast carcinomas, particularly lobular carcinomas.
NKX3.1 is a highly sensitive and specific marker for prostate adenocarcinoma in line with other prostate markers like Prostate Specific Antigen (PSA) and Prostein (p501S), particularly useful in low differentiated tumours where PSA and/or Prostein may be weakly expressed or lost. NKX3.1 is a nuclear marker, which occasionally may allow for an easier interpretation than the above mentioned cytoplasmic markers.
Testis and normal prostate seem to be recommendable as positive tissue controls. Virtually all luminal epithelial cells lining the prostate glands must show a moderate to strong and distinct nuclear staining reaction. In testis, a weak to moderate nuclear staining reaction must be seen in dispersed spermagonia of the seminiferous tubules. Testis seems to be the preferred positive tissue control as the spermagonia express low-levels NKX3.1. Prostate is less reliable as positive tissue control for NKX3.1, since the luminal epithelial cells express high-level NKX3.1, making it difficult to evaluate the sensitivity and consistency of the protocol used. Appendix or colon can be used as negative tissue control for NKX3.1, in which no nuclear staining reaction should be seen. Internal NordiQC data have indicated that the NKX3.1 antigen is influenced by pre-analytical conditions. Frequently, a staining gradient in prostate resection materials has been seen, which most likely is caused by delayed fixation and degrading of NKX3.1.