NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Although most studies have shown that staining for NKX3.1
protein is positive in the majority of primary prostatic
adenocarcinomas, it has been shown to be downregulated in many high-grade
prostate cancers, and completely lost in the majority of metastatic
prostate cancers (eg, in 65% to 78% of lesions). A recent study showed that NKX3.1 staining with a novel antibody was highly sensitive and specific for high-grade prostatic
adenocarcinoma when compared with high-grade urothelial
carcinoma. This raised the question that this antibody may perform better than earlier used
antibodies in metastatic prostate
tumors. However, the sensitivity and specificity for prostate
carcinomas for this antibody in metastatic lesions was not determined. Although
prostate-specific antigen (PSA) and
prostatic-specific acid phosphatase (PSAP) are excellent tissue markers of
prostate cancer, at times they may be expressed at low levels, focally, or not at all in poorly differentiated primary and metastatic prostatic
adenocarcinomas. The purpose of this study was to determine the performance of NKX3.1 as a marker of metastatic
adenocarcinoma of prostatic origin. Immunohistochemical staining against NKX3.1, PSA, and PSAP was carried out on a tissue microarray (TMA) (0.6-mm tissue cores) of
hormone naïve metastatic prostate
adenocarcinoma specimens from lymph nodes, bone, and soft tissue. To determine the specificity of NKX3.1 for prostatic
adenocarcinoma, we used TMAs that contained
cancers from various sites including the urinary bladder, breast, colon, salivary gland, stomach, pancreas, thyroid, and central nervous system, and standard
paraffin sections of
cancers from other sites including the adrenal cortex, kidney, liver, lung, and testis. Overall 349 nonprostatic
tumors were evaluated. Any nuclear staining for NKX3.1 was considered positive and the percentage of cells with nuclear staining and their mean intensity level were assessed visually. Sensitivity was calculated by considering a case positive if any TMA core was positive. The sensitivity for identifying metastatic prostatic
adenocarcinomas overall was 98.6% (68/69 cases positive) for NKX3.1, 94.2% (65/69 cores positive) for PSA, and 98.6% (68/69 cores positive) for PSAP. The specificity of NKX3.1 was 99.7% (1/349 nonprostatic
tumors positive). The sole positive nonprostatic
cancer case was an invasive
lobular carcinoma of the breast. NKX3.1 seems to be a highly sensitive and specific tissue marker of metastatic prostatic
adenocarcinoma. 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.