Heterogeneity of Prostate-Specific Membrane Antigen (PSMA) Expression in Prostate Carcinoma with Distant Metastasis

Mannweiler, Sebastian; Amersdorfer, Peter; Trajanoski, Slave; Terrett, Jonathan; King, D. H.; Méhes, Gábor

doi:10.1007/s12253-008-9104-2

Cited by 332 publications

(252 citation statements)

References 15 publications

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“…Other authors also reported a high sensitivity of 85-100% in lymph node and distant metastases. 30,31 Until a few years ago, detection of TMPRSS2-ERG fusion was only possible using fluorescence in situ hybridization. Since TMPRSS2-ERG fusion highly correlates with ERG overexpression, the newly available monoclonal antibodies displaying ERG overexpression open up the opportunity for routine utilization.…”

Section: Discussionmentioning

confidence: 99%

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Queisser¹,

Hagedorn²,

Braun³

et al. 2015

Modern Pathology

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Prostate cancer is mostly diagnosed at an early stage; however, some tumors are diagnosed in a metastatic stage as cancer of unknown primary origin. In order to allow specific treatment in the case of prostate cancer presenting as cancer of unknown primary origin, it is important to determine the tumor origin. Prostate-specific antigen is used as a diagnostic marker for prostate cancer but the expression declines with progression to castration-resistant prostate cancer. Aim of this study was to identify the most informative marker constellation, which is able to detect metastatic prostate cancer at high sensitivity. The widely used prostate cancer markers such as prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene were investigated for their sensitivity to detect prostatic origin of metastases. Expression of prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene was determined on archived tissue specimens consisting of benign prostatic tissue (n ¼ 9), primary prostate cancer (n ¼ 79), lymph node metastases (n ¼ 58), and distant metastases (n ¼ 39) using immunohistochemistry. The staining intensity was categorized as negative (0), weak (1), moderate (2), and strong (3). All markers except ETS-related gene were able to detect at least 70% of lymph node metastases and distant metastases, with prostate-specific antigen, androgen receptor, and prostate-specific membrane antigen having the highest sensitivity (97%, 91%, and 94%, respectively). A further increase of the sensitivity up to 98% and 100% could be achieved by the combination of prostate-specific antigen, prostate-specific membrane antigen, or androgen receptor for lymph node metastases and for distant metastases, respectively. The same sensitivity could be reached by combining prostate-specific membrane antigen and prostein. Our data show that a combined staining of at least two prostate markers should be utilized to identify metastases as originating from prostate cancer. Modern Pathology (2015) 28, 138-145; doi:10.1038/modpathol.2014 published online 13 June 2014 Prostate cancer is the most commonly diagnosed non-epidermal cancer and second-most common cancer-related cause of death in men in the western world. 1 The patients' death is often caused by the development of castration-resistant prostate cancer. Most prostate cancers are detected early in a localized stage; however, in some cases, metastases can be the first manifestation of a prostate cancer. 2 Unlike other carcinomas, hormone-sensitive prostate cancer responds to hormonal therapy and therefore the identification of the tumor origin is important in order to allow specific treatment. Male patients with a metastatic adenocarcinoma are routinely assessed for prostatic origin using prostate-specific immunohistochemistry markers like prostate-specific antigen (PSA). 3 PSA is highly expressed in benign prosta...

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Section: Discussionmentioning

confidence: 99%

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Queisser¹,

Hagedorn²,

Braun³

et al. 2015

Modern Pathology

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“…However, especially in patients with PSA values below 3 ng/mL, the detection rate is only 40%-60% (3,4,7). Recently, a new molecular probe targeting, for example, the gastrinreleasing peptide receptor or the prostate-specific membrane antigen (PSMA), has been developed (10)(11)(12). PSMA is a membrane-bound enzyme with significantly elevated expression in PC cells in comparison to benign prostatic tissue (13).…”

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Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy

et al. 2015

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The expression of prostate-specific membrane antigen (PSMA) is increased in prostate cancer. Recently, 68 Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)]) was developed as a PSMA ligand. The aim of this study was to investigate the detection rate of 68 Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy. Methods: Two hundred forty-eight of 393 patients were evaluable for a retrospective analysis. Median prostate-specific antigen (PSA) level was 1.99 ng/mL (range, 0.2-59.4 ng/mL). All patients underwent contrast-enhanced PET/CT after injection of 155 ± 27 MBq of 68 Ga-PSMA ligand. The detection rates were correlated with PSA level and PSA kinetics. The influence of antihormonal treatment, primary Gleason score, and contribution of PET and morphologic imaging to the final diagnosis were assessed. Results: Two hundred twenty-two (89.5%) patients showed pathologic findings in 68 Ga-PSMA ligand PET/CT. The detection rates were 96.8%, 93.0%, 72.7%, and 57.9% for PSA levels of $2, 1 to ,2, 0.5 to ,1, and 0.2 to ,0.5 ng/mL, respectively. Whereas detection rates increased with a higher PSA velocity (81.8%, 82.4%, 92.1%, and 100% in ,1, 1 to ,2, 2 to ,5, and $5 ng/mL/y, respectively), no significant association could be found for PSA doubling time (82.7%, 96.2%, and 90.7% in .6, 4-6, and ,4 mo, respectively). 68 Ga-PSMA ligand PET (as compared with CT) exclusively provided pathologic findings in 81 (32.7%) patients. In 61 (24.6%) patients, it exclusively identified additional involved regions. In higher Gleason score (#7 vs. $8), detection efficacy was significantly increased (P 5 0.0190). No significant difference in detection efficacy was present regarding antiandrogen therapy (P 5 0.0783). Conclusion: Hybrid 68 Ga-PSMA ligand PET/CT shows substantially higher detection rates than reported for other imaging modalities. Most importantly, it reveals a high number of positive findings in the clinically important range of low PSA values (,0.5 ng/mL), which in many cases can substantially influence the further clinical management.

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“…PSMA is a transmembrane protein that is highly overexpressed (100-to 1,000-fold) on almost all PC tumors (16)(17)(18)(19). Only 5%-10% of primary PC lesions have been shown to be PSMA-negative (20,21).…”

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PSMA Ligands for PET Imaging of Prostate Cancer

et al. 2017

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Heterogeneity of Prostate-Specific Membrane Antigen (PSMA) Expression in Prostate Carcinoma with Distant Metastasis

Cited by 332 publications

References 15 publications

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy

PSMA Ligands for PET Imaging of Prostate Cancer

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Heterogeneity of Prostate-Specific Membrane Antigen (PSMA) Expression in Prostate Carcinoma with Distant Metastasis

Cited by 332 publications

References 15 publications

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

Evaluation of Hybrid 68Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy

PSMA Ligands for PET Imaging of Prostate Cancer

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Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy