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.

Multimodality Imaging of Prostate Cancer

“…The pooled detection rate was 70.2% for the entire cohort, ranging from 44.9% for a PSA level of less than 0.5 ng/mL to 93.9% for a PSA level of at least 2 ng/mL on stratified subgroup analysis. All the studies showed a maximal detection rate at a PSA level of at least 2 ng/mL, with rates of around 90%, as is consistent with the fact that around 5%-10% of PCa do not overexpress PSMA and are thus PSMA-negative (70). The authors concluded that PSMAtargeted radiotracers are likely effective for the detection of BCR at low PSA levels, but there was significant study heterogeneity (I 2 of 95.6% for the entire cohort) due to differences in inclusion criteria, study populations, methodology, radiotracers used, retrospective designs, and reference standards.…”

Prostate-specific membrane antigen in circulating tumor cells is a new poor prognostic marker for castration-resistant prostate cancer

“…PSMA was reported to promote cancer progression and malignant transformation at least in part via neovascularization [12,13]. Immunohistochemical analysis revealed increased PSMA expression in primary and metastatic lesions of prostate cancer compared with normal prostate, and PSMA expression was reported to correlate with Gleason score and cancer aggressiveness [13,14] [26]. As opposed to these data, in this study, there was no significant association between Gleason score and PSMA expression in CTC ( Table 2), suggesting that PSMA in CTCs is an independent poor prognostic marker.…”

Synthesis and Evaluation of 99mTc-Tricabonyl Labeled Isonitrile Conjugates for Prostate-Specific Membrane Antigen (PSMA) Image

“…PSMA is expressed in most PCa tissues and its expression often increased in metastatic, poorly differentiated, androgen-independent, and hormone-refractory carcinoma [2][3][4]. In addition, the levels of PSMA expression correlate with the progression, stage, and the risk of disease [5,6]. Therefore, PSMA is considered to be a promising, reliable, and an efficient biomarker for PCa imaging and therapeutic application.…”