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

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.

[68 Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma

“…A previously published limited immunohistochemistry study showed that 74–80% of HCC tumors presented moderate-to-strong staining for PSMA, while completely negative staining was seen in only 4–26% of samples [ 11 , 19 ]. All studies showed PSMA expression in the neovascular structures [ 11 , 12 , 19 ].…”

“…A previously published limited immunohistochemistry study showed that 74–80% of HCC tumors presented moderate-to-strong staining for PSMA, while completely negative staining was seen in only 4–26% of samples [ 11 , 19 ]. All studies showed PSMA expression in the neovascular structures [ 11 , 12 , 19 ]. Tolkach et al [ 19 ] also reported PSMA expression on the canalicular membrane within the liver, but no expression was detected in the vasculature of the surrounding normal liver tissue.…”

Radiolabelled PSMA PET/CT or PET/MRI in hepatocellular carcinoma (HCC): a systematic review

“…The majority of HCC shows high levels of PSMA expression on tumor vessels and on canalicular membrane of cells [26,28] and therefore important implications for PSMAtargeted imaging and therapy arise. PSMA-targeted imaging of HCC in clinical practice has been evaluated only by a few studies and most of these studies are case reports [22,23,[27][28][29][30][31][32][33][34], probably because of the small number of centers that currently use radiolabelled PSMA PET/CT or PET/ MRI, resulting in a reduction of the population of patients overall studied.…”

“…A total of 55 articles were extrapolated with the computer literature search and by reviewing the titles and abstracts 43 of them were excluded because the reported data were not within the field of interest of this review. Twelve articles were selected and retrieved in full-text version [22][23][24][25][26][27][28][29][30][31][32][33]; one additional study was found screening the references of these articles [34]. A total of 13 articles were then included in the systematic review [22][23][24][25][26][27][28][29][30][31][32][33][34] (Fig.…”

Advances in Development of Radiometal Labeled Amino Acid-Based Compounds for Cancer Imaging and Diagnostics

“…From the cancerous cells, it is primarily expressed in benign and malignant prostatic tissue [ 192 ]. However, studies on the PSMA-expression in also other tumor types are available, including breast, gastric, and colorectal cancer, lung and renal carcinoma, and brain tumors [ 193 , 194 , 195 , 196 , 197 , 198 ]. Thus, PSMA has become one of the most promising and extensively evaluated molecular targets in nuclear medicine.…”