EAU 2018: Prostate Specific Membrane Antigen (PSMA) Expression in Transitional Cell Carcinoma (TCC) – Who Puts The S in PSMA?

Copenhagen, Denmark (UroToday.com) PSMA (prostate-specific membrane antigen) is a unique molecular specific to prostate tissue that has enabled novel imaging for prostate cancer, specifically in the setting of biochemical recurrence. PSMA-targeted PET scans, used for both diagnosis and potentially treatment, have been increasingly utilized in the setting of early biochemical recurrence, and in some cases, for staging purposes. As such, it has revolutionized prostate cancer management.

However, contrary to its name, previous studies have shown that the expression of PSMA is not as specific to prostate tissue as its name suggests. Indeed, PSMA PET scans often light up the parotid gland, and other organs may contain lower levels of PSMA – making it not as specific to prostate tissue as we thought.

In this study, the authors examine the expression of PSMA in different transitional cell carcinoma (TCC) / urothelial carcinoma stages. Bladder cancer has been found to cross-express some other prostate specific molecules, including the androgen-receptor. Hence, it is not surprising that it may express PSMA as well.

They completed immunhistochemical (IHC) PSMA staining on 124 TCC samples (primary and metastatic tissue) using an established PSMA antibody (folate hydrolase (prostate-specific membrane antigen) 1 (FOLH1), epitope: AA 44-750, extracellular domain). PSMA expression in tumor tissue, adjacent normal tissue and blood vessels was determined by a uro-pathologist using a 0-4 staining grade (0=no staining, 1=0%-25%, 2=25%-30%, 3=50%-75%, 4>75%). Results were correlated with patient data (age, sex, TNM, grading).

Bladder cancer tissue showed a significantly higher PSMA expression compared to adjacent normal urothelium (p<0.001). Interestingly, NMIBC (n=72) revealed significantly higher PSMA expression compared to muscle invasive bladder cancer (n=33, p<0.05). PSMA expression also significantly differed between the various T-stages (p<0.05) and tumor differentiation (p<0.001).

Looking at metastatic disease, 71% (n=31) of metastatic TCC tissues showed a different PSMA expression than the primary lesion – but it was not specified if it was higher or lower expression. In blood vessels, PSMA was detectable in 85% of tissue.

No gender specific significant differences were found. This implies that PSMA was present in the bladder of female patients as well.

In this very interesting study, the authors demonstrate that bladder cancer tissue, normal urothelial tissue and blood vessels express PSMA at different levels, but it is present in all of them. A significantly higher PSMA expression is found in bladder cancer tissue than in normal urothelium, but it is actually highest in non-muscle invasive disease! These first results make PSMA a promising target for diagnosis and therapy of TCC. To what extent PSMA can be used in TCC will have to be subject of further study.

However, what would have been interesting is to run a reference of prostate cancer tissue to showcase the relative expression of bladder and bladder cancer compared to prostate cancer. This may help provide some information about the clinical utility of PSMA.

Speaker: H. Schreiber

Co-Authors: Nimphius W., Verburg F., Luster M., Hofmann R., Hegele A.

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd, at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark
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