Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression

NKX3.1 is a prostate-specific homeobox gene located on chromosome 8p21, In the mouse, Nkx3.1 has growth-suppressive and differentiating effects on pro static epithelium. Mutations of the coding region of NKX3.1 were not found in human prostate cancer, failing to support the notion that NKX3.1 was a t umor suppressor gene. To study the expression of NKX3.1 protein in human ti ssues and prostate cancer, we derived a rabbit antiserum against purified r ecombinant NKX3.1, Among normal human tissues, NKX3.1 expression was seen i n testis, in rare pulmonary mucous glands, and in isolated regions of trans itional epithelium of the ureter, NKX3.1 was uniformly expressed in nuclei of normal prostate epithelial cells in 61 histological sections from radica l prostatectomy specimens. We analyzed 507 samples of neoplastic prostate e pithelium, most of which were contained on a tissue microarray that contain ed samples from different stages of prostatic neoplasia. We observed comple te loss of NKX3.1 expression in 5% of benign prostatic hyperplasias, 20% of high-grade prostatic intraepithelial neoplasias, 6% of T1(a/b) samples, 22 % of T3/4 samples, 34% of hormone-refractory prostate cancers, and 78% of m etastases, Our data show that NKX3.1 expression is highly, but not exclusiv ely, specific for the prostate. Loss of NKX3.1 expression is strongly assoc iated with hormone-refractory disease and advanced tumor stage in prostate cancer (P < 0.0001).