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

Wei Chen, Zhenghong Lee, Amad Awadallah, Lan Zhou, Wei Xin, Wei Chen, Zhenghong Lee, Amad Awadallah, Lan Zhou, Wei Xin

Abstract

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.

Keywords: Cholangiocarcinoma; Diagnostic marker; Metastatic pancreatic ductal adenocarcinoma; PSMA; Peritumoral expression.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Prostate adenocarcinoma showed PSMA positivity in tumor cell pattern. a. Primary prostate adenocarcinoma (PSMA, 200x); b. Metastatic prostate adenocarcinoma (PSMA, 200x); c, d. Metastatic prostate adenocarcinoma (C. HE, 200x; D. PSMA, 200x)
Fig. 2
Fig. 2
Primary cholangiocarcinoma and metastatic pancreatic ductal adenocarcinoma. a. Primary cholangiocarcinoma (HE, 100x); b. CD34 expression in cholangiocarcinoma (CD34, 200x); c. PSMA peritumoral/vascular expression in cholangiocarcinoma (PSMA, 200x). d. Metastatic pancreatic ductal adenocarcinoma in liver (HE, 100x) e. CD34 expression in pancreatic ductal adenocarcinoma (CD34, 200x); f. PSMA is negative in metastatic pancreatic ductal adenocarcinoma (PSMA, 200x)

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