The prostein gene encodes a 553-amino acid type IIIa plasma membrane protein with a cleavable signal peptide and 11 transmembrane-spanning regions (1). IHC analysis has demonstrated that the Prostein antibody (also known as P501S) was expressed in the normal prostate tissue and the vast majority of malignant prostatic tissues, regardless of grade and metastatic status (2). Prostein expression was not detected in thousands of representative normal and malignant non-prostatic tissue samples (2). Prostein has a perinuclear-like staining pattern, as expression is found in the Golgi complex of prostate cells. Compared to the PSA antibody, prostein was positive in 99% of metastatic prostate adenocarcinomas while 97% of cases were positive for PSA. No tumor was negative for both markers (3).
Prostate specific antigen (PSA) is a chymotrypsin-like serine protease (kallikrein family) produced by the prostate epithelium. Studies have shown that PSA is highly specific and is used to confirm prostatic acinar cell origin in primary and metastatic carcinomas, and to rule out non-prostatic carcinoma mimics (4-5).
NKX3.1 is a nuclear protein encoded by the NKX3-1 gene located on chromosome 8p. NKX3.1 protein has been found to be expressed in the vast majority of primary prostatic adenocarcinomas with 99.7% specificity. Contrary to earlier studies, NKX3.1 positive staining has now been shown to be highly sensitive and specific for high-grade prostatic adenocarcinomas vs. high-grade urothelial carcinomas. In addition, the sensitivity for identifying metastatic prostatic adenocarcinomas overall was 98.6% (68/69) for NKX3.1 and 94.2% (65/69) for PSA (6).
The International Society of Urological Pathology suggests the use of Prostein and NKX3.1 in addition to PSA, p63 and CK HMW as prostate markers (7). The CK HMW with p63 and AMACR are useful for atypical glands suspicious for adenocarcinoma of the prostate. GATA3 may be used along with PSA to differentially diagnose urothelial carcinoma (7).
Each antibody in this triple antibody cocktail can be morphologically identified in prostate cancers as PSA is a cytoplasmic stain, Prostein is present in the Golgi apparatus with perinuclear staining and NXK3.1 is a nuclear stain. Simultaneous stains with PSA, Prostein and NKX3.1 may greatly improve the detection rate and identification of a significant majority of prostatic metastases, especially poorly differentiated carcinomas of an unknown primary (7).