TY - JOUR
T1 - Prostate-specific membrane antigen expression in hepatocellular carcinoma
T2 - Potential use for prognosis and diagnostic imaging
AU - Tolkach, Yuri
AU - Goltz, Diane
AU - Kremer, Anika
AU - Ahmadzadehfar, Hojjat
AU - Bergheim, Dominik
AU - Essler, Markus
AU - Lam, Marnix
AU - De Keizer, Bart
AU - Fischer, Hans Peter
AU - Kristiansen, Glen
N1 - Funding Information:
No financial support was received for this work.
Publisher Copyright:
© Tolkach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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 68Ga-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.
AB - 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 68Ga-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.
KW - FOLH1
KW - Hepatocellular carcinoma
KW - PET/CT
KW - Prostate-specific membrane antigen
KW - Theranostic
UR - http://www.scopus.com/inward/record.url?scp=85068155567&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.27024
DO - 10.18632/oncotarget.27024
M3 - Article
C2 - 31289613
AN - SCOPUS:85068155567
SN - 1949-2553
VL - 10
SP - 4149
EP - 4160
JO - Oncotarget
JF - Oncotarget
IS - 41
ER -