ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Oncology in Veterinary Medicine
Volume 12 - 2025 | doi: 10.3389/fvets.2025.1552345
Immunohistochemical characterization and potential prognostic relevance of dopamine signaling in canine pulmonary adenocarcinoma
Provisionally accepted
Alana Roth Kuzmik1,2*
Davis Seelig1,3
Luke Hoeppner3,4
Aaron Rendahl1Hannah Able1,5Amber Wolf-Ringwall1,6
Jessica Lawrence1,3,7,8*- 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, United States
- 2VCA Bay Area Veterinary Specialists and Emergency Hospital, San Leandro, United States
- 3Masonic Cancer Center, Medical School, University of Minnesota, Minneapolis, Minnesota, United States
- 4The Hormel Institute, University of Minnesota Twin Cities, Austin, Minnesota, United States
- 5VCA Aurora Animal Hospital, Aurora, United States
- 6Red River Animal Emergency Hospital & Referral Center, Fargo, United States
- 7Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, United States
- 8Department of Radiation Oncology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States
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Dopamine signaling contributes to tumor progression in human lung adenocarcinoma. Isoforms of dopamine-and-cAMP-regulated phosphoprotein Mr 32000 (DARPP-32) are overexpressed in human lung adenocarcinoma and are associated with prognosis and development of treatment resistance. Despite similarities to human lung adenocarcinoma, dopamine signaling has not yet been evaluated in canine pulmonary adenocarcinoma. The objective of this study was to characterize immunohistochemical expression of DARPP-32 isoforms in canine pulmonary adenocarcinoma and assess associations with clinical variables, markers of proliferation and angiogenesis, and outcome. Immunohistochemistry for DARPP-32 isoforms DARPPN and DARPPC, EGFR, D2R, and VEGFR2 was used to assess 46 canine adenocarcinomas. The percentage of tumor cells positive for target protein expression and staining intensity of DARPPC, DARPPN, and EGFR were quantified using a modified immunohistochemical scoring scheme. Intratumoral vascular endothelial D2R and VEGFR2 expression were quantified based on the number of positive vessels. DARPPN or DARPPC was expressed in 40 (87%) adenocarcinomas; 54% of tumors expressed both isoforms. DARPPN was positively correlated with tumor volume, VEGFR2 expression and mitotic count. DARPPC was positively correlated with EGFR expression. VEGFR2 expression was positively correlated to EGFR expression and mitotic count. When stratified by the median, survival was shorter with increased tumor volume (p=0.003) and greater intratumoral VEGFR2 expression (p=0.042). Dogs with DARPPN (p=0.059) or DARPPC (p=0.120) expression greater than the median had shorter survival than those with lower expression. Collectively, data support further investigation of DARPP-32 protein signaling in canine lung adenocarcinoma.
Keywords: Cancer, Dopamine, Adenocarcinoma, EGFR, VEGFR2, pulmonary, Lung, signaling
Received: 27 Dec 2024; Accepted: 14 Aug 2025.
Copyright: © 2025 Kuzmik, Seelig, Hoeppner, Rendahl, Able, Wolf-Ringwall and Lawrence. 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:
Alana Roth Kuzmik, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, 55108, Minnesota, United States
Jessica Lawrence, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, California, United States
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