Immunohistochemical Evaluation of SARS-CoV Nucleoprotein and ACE2 Markers in Testicular Tumors Diagnosed During the COVID-19 Pandemic

Abstract

Background: The incidence of testicular tumors during the COVID-19 pandemic has raised questions about the potential impact of viral infection on tumor development. This study aimed to explore the relationship between COVID-19 and testicular tumors through a retrospective analysis of 32 cases diagnosed before and during the pandemic. Methods: A total of 32 testicular tumors were analyzed, with distribution based on the year of diagnosis. Immunohistochemical studies were conducted to assess SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) expression in tumor cells. Results: The highest frequency of tumor diagnoses was observed in 2021 (19.4%), with a notable increase in diagnoses in 2022 compared with pre-pandemic years. No significant correlation was found between COVID-19 infection and tumor types (P = .476). The distribution of seminoma and mixed germ cell tumors (MGCT) was similar in both periods. Strong SARS-CoV-2 antibody positivity was found in 11 cases, with expression primarily in Leydig cells and some in Sertoli and plasma cells. The difference in SARS-CoV-2 expression between periods was statistically significant (P = 0013). The ACE2 expression was observed in all tumor groups, but statistical analysis was not significant. Conclusion: The presence of SARS-CoV-2 nucleoprotein in the tumor microenvironment, particularly during the pandemic, suggests an indirect role of the virus in the development of testicular tumors. Although SARS-CoV-2 does not exhibit direct oncogenic effects, its presence could influence tumorigenesis through mechanisms like inflammation and oxidative stress. The ACE2 expression further supports the hypothesis that the virus may trigger adaptive changes in tumor cells. The SARS-CoV-2 could act as a co-factor in tumor progression, especially in individuals predisposed to testicular tumors. © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).