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

Tolkach, Yuri; Goltz, Diane; Kremer, AE; Ahmadzadehfar, Hojjat; Bergheim, Dominik; Essler, Markus; Lam, M; Keizer, Bart de; Hp, Fischer; Kristiansen, Glen

doi:10.1055/s-0038-1677237

Cited by 5 publications

(15 citation statements)

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“…Tumor cell PSMA expression was mainly reported in both benign and malignant prostate tissue, while neovascular expression was found in a wider spectrum of malignant neoplasms [ 6 , 7 , 9 , 10 ]. Chang et al identified high frequency of neovascular expression in epithelial tumors (such as carcinomas, including renal cell carcinoma, transitional cell carcinoma, pancreatic ductal adenocarcinoma, breast carcinoma and colonic adenocarcinoma), neuroendocrine tumors, melanoma, and non-vascular soft tissue sarcomas [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…In our study showed, 68% of the cases of HCC had neovascular PSMA expression, consistent with previous studies. However, the positive rates among previous reports showed disagreement [ 7 , 10 , 14 ]. Tolkach et al reported more than 80% of tumors showed vascular expression in 158 cases of HCC [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, the positive rates among previous reports showed disagreement [ 7 , 10 , 14 ]. Tolkach et al reported more than 80% of tumors showed vascular expression in 158 cases of HCC [ 10 ]. However, in another analysis, the author found weak PSMA expression in only 3 out of 44 HCC cases (6.8%) [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

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Peritumoral/vascular expression of PSMA as a diagnostic marker in hepatic lesions

et al. 2020

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Background The differential diagnosis between primary cholangiocarcinoma and metastatic pancreatobiliary adenocarcinoma is histologically challenging due to lack of distinct morphological features and reliable molecular markers. Prostate-specific membrane antigen (PSMA) is expressed in prostate epithelium and upregulated on the surface of prostatic adenocarcinoma cells. Studies have shown PSMA enzymatic activity is involved in malignancy-driven neoangiogenesis in the endothelium of tumor-associated neovasculature in breast, lung, thyroid, hepatocellular carcinoma (HCC) and urothelial cancer. Recently, PSMA-targeted imaging technology (PSMA PET-CT) detected the presence of PSMA in primary cholangiocarcinoma. However histological correlation with PSMA expression other mass lesions in the liver has not yet been studied. Methods 72 cases of liver mass resection were collected at a tertiary hospital from 2011 to 2019. Immunohistochemical stains for PSMA and CD34 were performed. The expression of PSMA in tumor cells and associated neovascular endothelium were analyzed separately and the locations of vascular structures were confirmed by CD34 expression. Results Among 72 cases, 28 cases (22/72, 38.9%) showed PSMA peritumoral/vascular expression only, 3 cases (3/72, 4.2%) showed tumor cell expression only, and 2 cases (2/72, 2.8%) showed both tumor cell and peritumoral/vascular expression. The remainder (39/72, 54.2%) showed no expression. Particularly, most of primary cholangiocarcinoma showed PSMA vascular expression (13/15, 86.7%), while none of the 18 cases of metastatic pancreatobiliary adenocarcinoma were positive for PSMA (0/18, 0%) ( p < 0.01). Outside of pancreatobiliary adenocarcinoma, none of the metastatic tumors, including colon and lung cancers, expressed PSMA. In 8 cases of metastatic prostate carcinoma, 3 showed PSMA expressions in tumor cells only (3/8, 37.5%) and 2 expressed PMSA in both tumor cells and neovasculature (2/8, 25.0%). Out of 22 HCC cases, 15 (15/22, 68.2%) were positive for PSMA in tumor vasculature. None of the 5 hepatic adenoma expressed PSMA (0/5, 0%). Conclusion Significantly enhanced tumor-associated neovascular PSMA expression was identified in primary cholangiocarcinoma, compared to metastatic pancreatobiliary adenocarcinoma. Our findings potentially provide a sensitive marker in differential diagnosis between otherwise morphologically indistinguishable cases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Peritumoral/vascular expression of PSMA as a diagnostic marker in hepatic lesions

et al. 2020

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“…Immunohistochemical PSMA expression has been examined in 282 primary HCC tissue samples (Table 1) [91][92][93][94].…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

“…Overall, PSMA expression was mostly observed in the tumor-associated neovasculature (83%-235/282), and it was associated with poor prognosis in patients with HCC [91]. Only one of the studies also identified some PSMA expression by the tumor parenchyma (41% of samples), in a canalicular pattern [93].…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports

Uijen¹,

Derks

Merkx³

et al. 2021

Eur J Nucl Med Mol Imaging

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In the past decade, a growing body of literature has reported promising results for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy in prostate cancer. First clinical studies evaluating the efficacy of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) demonstrated favorable results in prostate cancer patients. [177Lu]Lu-PSMA is generally well tolerated due to its limited side effects. While PSMA is highly overexpressed in prostate cancer cells, varying degrees of PSMA expression have been reported in other malignancies as well, particularly in the tumor-associated neovasculature. Hence, it is anticipated that PSMA-RLT could be explored for other solid cancers. Here, we describe the current knowledge of PSMA expression in other solid cancers and define a perspective towards broader clinical implementation of PSMA-RLT. This review focuses specifically on salivary gland cancer, glioblastoma, thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, lung cancer, and breast cancer. An overview of the (pre)clinical data on PSMA immunohistochemistry and PSMA PET/CT imaging is provided and summarized. Furthermore, the first clinical reports of non-prostate cancer patients treated with PSMA-RLT are described.

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PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68Ga‐PSMA‐11 PET Using Cyclotron‐Produced 68Ga

et al. 2021

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Prostate‐specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68 Ga‐PSMA‐11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68 Ga‐PSMA‐11 PET was prospectively performed in patients with treatment‐naïve HCC on a digital PET scanner using cyclotron‐produced 68 Ga. Uptake was graded qualitatively and semi‐quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA ( P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor‐associated neovasculature. Higher tumor grade was associated with PSMA expression ( P = 0.012) but there was no association with tumor size ( P = 0.14), fibrosis ( P = 0.35), cirrhosis ( P = 0.74), hepatitis B virus ( P = 0.31), or hepatitis C virus ( P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10 ‐5 ) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = −0.753; P = 1.58 × 10 ‐6 ). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68 Ga‐PSMA‐11 standardized uptake value: SUV max (median [range] 9.2 [4.9‐28.4]), SUV mean 4.7 (2.4‐12.7), and tumor‐to‐liver background ratio 2 (1.1‐11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68 Ga‐PSMA‐11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.

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

Cited by 5 publications

References 14 publications

Peritumoral/vascular expression of PSMA as a diagnostic marker in hepatic lesions

Peritumoral/vascular expression of PSMA as a diagnostic marker in hepatic lesions

PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports

PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68Ga‐PSMA‐11 PET Using Cyclotron‐Produced 68Ga

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