PSMA Expression: A Potential Ally for the Pathologist in Prostate Cancer Diagnosis

Prostate cancer (PCa) is the second most common cancer in males. Prostate-specific antigen (PSA) level is useful to define patient treatment and follow-up but has some limitations when used for diagnostic/prognostic purposes. Patients with PCa are currently stratified on the basis of the Gleason score. Prostate-specific membrane antigen (PSMA) is a non-soluble type 2 integral membrane protein, with carboxypeptidase activity, weakly expressed in normal prostate tissue but strongly expressed in cancer. Although it has been shown that PSMA plays a functional role in PCa progression, its correlation with the Gleason score and PSA has yet to be clarified.

At Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST -IRCCS), a Cancer Centre in Romagna, we aim to classify PCa patients according to PSMA expression. Our research shows that PSMA increases as tumor grade (Gleason score) increases, and this finding could potentially be used by pathologists to classify tumors on the basis of cellular morphology alone. The tumors morphologically classified as Gleason pattern 3 showing high PSMA expression may be more aggressive. Thus, analyzing PSMA by immunohistochemistry could facilitate patient stratification. In particular, our study revealed lower PSMA expression in Gleason pattern 3 (Grade Group 1) compared to Gleason pattern 4 (Grade Group 2) or 5 (Grade Group 3), with a PSMA sensitivity of 84% and a specificity of 95%.

Moreover, given that the degree of uptake of 68 Ga-PSMA-11 in prostate cancer cells was found to correlate with PSMA expression, this biomarker may be useful for both therapeutic purposes and patient follow-up.

Written by: Dott.ssa Sara Bravaccini, PhD, Researcher, Laboratory of Biosciences, Cyto Histo Molecular Pathology, Scientific Institute of Romagna for the Study and the Treatment of Cancer ( IRST ) Srl IRCCS, Via Maroncelli, Meldola FC, Italy

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