Prostate-specific membrane antigen expression in hepatocellular carcinoma: potential use for prognosis and diagnostic imaging

// Yuri Tolkach 1 , Diane Goltz 1 , Anika Kremer 1 , Hojjat Ahmadzadehfar 2 , Dominik Bergheim 1 , Markus Essler 2 , Marnix Lam 3 , Bart de Keizer 3 , Hans-Peter Fischer 1 , § and Glen Kristiansen 1 , § 1 Institute of Pathology, University Hospital Bonn, Bonn 53127, Germany 2 Clinic of Nuclear Medicine, University Hospital Bonn, Bonn 53127, Germany 3 Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands § Shared senior co-authorship Correspondence to: Glen Kristiansen, email: glen.kristiansen@ukbonn.de Keywords: FOLH1 ; hepatocellular carcinoma; PET/CT; prostate-specific membrane antigen; theranostic Received: January 01, 2019 Accepted: May 26, 2019 Published: June 25, 2019 ABSTRACT Aim The prostate-specific membrane antigen (PSMA) is currently being established as a potent diagnostic marker in many tumor types. So far, its evidence in hepatocellular carcinoma (HCC) is sparse. The aim of our study was a comprehensive evaluation of PSMA expression and its prognostic role in patients with hepatocellular carcinoma as well as feasibility test of PSMA as an agent for diagnostic imaging. Methods The cohort for immunohistochemistry consisted of 153 patients with HCC. For validation purposes the HCC cohort (n = 359) of The Cancer Genome Atlas was analyzed on transcript level as well. Results On immunohistochemistry, non-tumorous liver tissue showed PSMA expression on canalicular membranes in all cases. In tumor tissue two patterns of expression, with a canalicular (41.1% of tumors) and a neovascular (89.9% of tumors) staining were seen. Completely negative for both two patterns were only 4.1% of tumors; conversely, 79.2% of the tumors showed high levels of PSMA protein expression at any location. At mRNA level higher FOLH1 (PSMA) expression rates were statistically significant and independently associated with longer overall survival times. Additionally, a case report of successful diagnostic 68 Ga-PSMA-11 PET/CT in a patient with HCC progression on multiple therapy lines is provided. Conclusions Majority of hepatocellular carcinomas show high levels of PSMA expression on tumor vessels and on canalicular membrane of the tumor cells. Putative diagnostic, prognostic and therapeutic value of PSMA in HCC warrants further clinically oriented investigations.