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ORIGINAL RESEARCH article

Front. Nucl. Med.
Sec. Radionuclide Therapy
Volume 4 - 2024 | doi: 10.3389/fnume.2024.1480471

Immunohistochemical basis for FAP as a candidate theranostic target across a broad range of cholangiocarcinoma subtypes

Provisionally accepted
Laura C Jorgenson Laura C Jorgenson 1Michael S Torbenson Michael S Torbenson 2Thorvardur R Halfdanarson Thorvardur R Halfdanarson 3Lionel A Kankeu Fonkoua Lionel A Kankeu Fonkoua 3Nguyen H Tran Nguyen H Tran 3Lewis R Roberts Lewis R Roberts 4Rory L Smoot Rory L Smoot 5Ajit H Goenka Ajit H Goenka 1Scott M Thompson Scott M Thompson 1*
  • 1 Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
  • 2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States
  • 3 Department of Oncology, Mayo Clinic, Rochester, Minnesota, United States
  • 4 Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States
  • 5 Department of Surgery, Mayo Clinic, Rochester, Massachusetts, United States

The final, formatted version of the article will be published soon.

    Purpose: The aims of this study were to evaluate and compare fibroblast activation protein (FAP) expression and localization in surgically resected cholangiocarcinoma (CCA), primary and metastatic hepatocellular carcinoma (HCC), hepatocellular adenoma (HCA), and focal nodular hyperplasia (FNH), and to identify any association between CCA clinical or pathologic features and FAP expression. Materials and Methods: FAP immunostaining from surgically resected CCA (N=58), primary intrahepatic and extrahepatic metastatic HCC (N=148), HCA (N26), and FNH (N=19) was scored (negative, weak positive, moderate positive or strong positive) from tissue microarrays. FAP expression was compared between groups. CCA FAP expression was compared to clinical and tumor pathology features. Results: Moderate-strong FAP expression in the tumor stroma was present in 93.1% of CCA, 60.7% of extrahepatic metastatic HCC, 29.6% of primary HCC, 21.1% of FNH, and 11.6% of HCA. Moderate-strong FAP expression in tumor stroma was significantly more prevalent in CCA than HCC (p<0.001), metastatic HCC (p=0.005), HCA (p<0.001) and FNH (p<0.001). FAP was expressed in the stroma of all but one CCA (1.7%), and FAP expression in CCA tumor stroma was not associated with any clinical or tumor pathology features (p>0.05, all). Conclusion: FAP is expressed in the stroma of a high proportion (93%) of primary CCA independent of patient clinical or tumor pathology features. As such, these data provide the tissue basis for systematically evaluating FAP as a theranostic target across a broad range of CCA subtypes.

    Keywords: cholangiocarcinoma (CCA), Fibroblast-activation protein (FAP), Liver Neoplasms, precision medicine, theranosctics

    Received: 14 Aug 2024; Accepted: 14 Nov 2024.

    Copyright: © 2024 Jorgenson, Torbenson, Halfdanarson, Kankeu Fonkoua, Tran, Roberts, Smoot, Goenka and Thompson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Scott M Thompson, Department of Radiology, Mayo Clinic, Rochester, MN 55905, Minnesota, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.