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Protein Expression, Amplification, and Mutation of HER2 Gene in Canine Primary Pulmonary Adenocarcinomas: Preliminary
Barbara Brunetti1, Dario de Biase2, Francesca Millanta3
1Department of Veterinary Medical Sciences, University of Bologna, 40126 Bologna, Italy.
Abstract:
Recently, human epidermal growth factor receptor 2 (HER2) has emerged as a therapeutic target of interest for non-small-cell lung cancer in humans. The role of HER2 in canine pulmonary adenocarcinomas is poorly documented. To address this gap, this study employed three methodologies: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) to investigate the protein expression, gene amplification, and mutation of HER2 in 19 canine primary pulmonary adenocarcinomas. By IHC, 3 out of 19 cases were overexpressed 3+, 6 were 2+, and 10 were negative. With FISH, 2 cases were amplified (12.5%), 3 were inadequate for the analyses, and the others were non-amplified. With NGS, seven cases were inadequate. All other cases were wild-type, except for one IHC 3+ case, which was amplified with FISH and with a specific mutation already described in human pulmonary adenocarcinoma, V659E. This mutation is probably sensitive to tyrosine kinase inhibitory drugs. These results are similar to those in human medicine and to the few data in the literature on canine lung carcinomas; the presence of 12.5% of amplified cases in dogs lays the foundation for future targeted drugs against HER2 alterations.
Insights
Human epidermal growth factor receptor 2 (HER2) is a potential target for canine lung cancer. This study found HER2 alterations in 12.5% of canine pulmonary adenocarcinomas, suggesting targeted therapies may be effective.
Area of Science:
- Veterinary Oncology
- Molecular Pathology
- Comparative Oncology
Background:
- Human epidermal growth factor receptor 2 (HER2) is a validated therapeutic target in human non-small-cell lung cancer.
- The role and prevalence of HER2 in canine pulmonary adenocarcinomas remain largely uncharacterized.
- Understanding HER2 in canine lung cancer can inform comparative oncology and potential therapeutic strategies.
Purpose of the Study:
- To investigate the protein expression, gene amplification, and mutation status of HER2 in canine pulmonary adenocarcinomas.
- To assess the potential of HER2 as a therapeutic target in canine lung cancer.
- To compare HER2 findings in dogs with those reported in human lung adenocarcinoma.
Main Methods:
- Immunohistochemistry (IHC) for HER2 protein expression analysis.
- Fluorescence in situ hybridization (FISH) for HER2 gene amplification detection.
- Next-generation sequencing (NGS) for identifying HER2 mutations.
Main Results:
- HER2 protein overexpression (3+) was observed in 3 of 19 cases via IHC.
- HER2 gene amplification was detected in 2 of 19 cases (12.5%) using FISH.
- One case exhibited both HER2 amplification and a V659E mutation, similar to human lung adenocarcinoma, suggesting potential drug sensitivity.
Conclusions:
- A subset of canine pulmonary adenocarcinomas harbors HER2 alterations, including amplification and specific mutations.
- The findings support the investigation of HER2-targeted therapies for canine lung cancer.
- This study provides a foundation for developing novel targeted treatments for canine lung carcinomas, drawing parallels with human medicine.
