Background: Prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), and NKX3.1 are sensitive and prostate-specific markers frequently used for the diagnosis of metastatic prostate cancer (mPCa). International Society of Urological Pathology recommends use of PSA as the initial immunohistochemical (IHC) marker to identify PCa. If the tumor is equivocal/weak/negative for PSA, then P501S and NKX3.1 stains are suggested. However, no specific studies have attempted to compare the staining sensitivity of these markers post specimen decalcification of bone specimens. In this study, we analyze the staining sensitivity of PSA, PSMA and NKX3.1 in bone specimens with mPCa after decalcification.
Design: We studied 24 cases of mPCa to the bone. All cases were decalcified for 24 to 48 hours prior to H&E staining and IHC workup. Eight cases were biopsies from vertebral bodies, five were from the femur, four came from the iliac bone, two were from ribs, three were from the pubic ramus, one was from the sacrum and one was from the skull. IHC staining pattern of PSA, PSMA and NKX3.1 was defined as follows: negative (no staining), focally positive (≤ 10%) and diffusely positive (≥ 10%). Focal and diffuse positivity are both considered positive.
Results: PSA was positive in 64% (14/22) cases, while PSMA and NKX3.1 were positive in all cases (17/17 and 24/24, respectively). The frequency of positive PSMA staining in decalcified samples of prostatic carcinoma metastatic to the bone is statistically higher than that of PSA staining, when analyzed by the Chi-square test (Chi-square statistic: 5.389; P = 0.0203). The frequency of positive NKX3.1 staining in decalcified samples of prostatic carcinoma metastatic to the bone is also statistically higher than that of PSA staining, when analyzed by the Chi-square test (Chi-square statistic: 10.56; P = 0.0012). When comparing PSMA and NKX3.1 positive staining, NKX3.1 tended to be diffusely positive at a higher frequency. However, this difference was not statistically significant.
Conclusion: This study demonstrates that PSMA and NKX3.1 are more sensitive markers than PSA for mPCa to the bone following decalcification. We recommend use of PSMA and NKX3.1, rather than PSA, as the IHC markers to confirm mPCa to the bone.
Keywords: NKX3.1; PSMA; bone metastasis; prostatic carcinoma.