NKX3.1 is a protein found in humans and is encoded by the NKX3.1 gene located on chromosome 8. The homeodomain containing transcription factor NKX3A is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner. NKX3.1 protein has been found to be positive in the vast majority of primary prostatic adenocarcinomas. A recent study showed that NKX3.1 staining was highly sensitive and specific for high-grade prostatic adenocarcinomas. The sensitivity for identifying metastatic prostatic adenocarcinomas overall was 98.6% (68/69 cases positive) for NKX3.1, and 94.2% (65/69 cores positive) for PSA. The specificity of NKX3.1 was 99.7% (1/349) in various cancers. NKX3.1 stains nuclei in both normal and prostate cancer, thus providing a robust stain that is easy-to-interpret, similar to other transcription factors such as TTF-1 or CDX2.
In the appropriate clinical setting, the addition of IHC staining for NKX3.1, along with other prostate-restricted markers, may prove to be a valuable adjunct to definitively determine prostatic origin in poorly differentiated metastatic carcinomas. NKX3.1 used in combination with ERG monoclonal antibody [9FY], may represent one of the most sensitive and specific markers for identifying tumors of prostatic origin.