PSMA expression: a potential ally for the pathologist in prostate cancer diagnosis

Abstract

Prostate cancer (PCa) patients are risk-stratified on the basis of clinical stage and PSA level at diagnosis and the Gleason Score (GS) in prostate biopsy. However, these parameters are not completely accurate in discriminating between high- and low-risk disease, creating a need for a reliable marker to determine aggressiveness. Prostate-specific membrane antigen (PSMA) appears to fulfill this need. We analyzed 79 prostate biopsies and 28 prostatectomies to assess whether PSMA expression detected by immunohistochemistry is related to GS. PSMA expression was correlated with GS in both sample types (biopsies, P < 0.0001 and prostatectomy samples, P = 0.007). We observed lower PSMA expression in Gleason pattern 3 than Gleason pattern 4, suggesting that this biomarker could be useful to distinguish between these entities (p < 0.0001). The best cut-off value of 45% immunopositivity was determined by receiver operating characteristic (ROC) curve analysis. In Gleason pattern 3 vs. Gleason pattern 4 and 5, PSMA sensitivity was 84.1% (95% CI 76.5%-91.7%) and specificity was 95.2% (95% CI 90.6%-99.8%), with an area under the curve of 93.1 (95% CI 88.8-97.4). Our results suggest that PSMA represents a potential ally for the pathologist in the diagnostic work-up of PCa to overcome long-standing morphological classification limits.

Figure 1

PSMA-positive PCa. (A) GS 6 (3 + 3, Grade Group 1) prostate adenocarcinoma (10 × magnification) with moderate endoluminal membrane staining. (B) GS 8 (4 + 4, Grade Group 4) prostate adenocarcinoma (10 × magnification) with strong membrane staining.

Figure 2

Restaging of a 46-year-old male with biochemical relapse after radical prostatectomy for high-risk PCa (Grade Group 4; PSA at diagnosis: 67.0 ng/mL). (A) PSMA PET MIP (maximum intensity projection) visualization showing PSMA-avid lymphadenopathy above and below the diaphragm. (B,C) PSMA PET/CT (transaxial and coronal views) showing intense PSMA uptake in a left retroclavicular node (SUVmax: 12.8). (D) PSMA expression in PCa cells in lymph node biopsy of the same patient (20 × magnification).