Related Experiment Video
Updated: Sep 15, 2025
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
TMPRSS2 Expression in Lung Tissue of Prostatic Adenocarcinoma Patients: A Pathologic Perspective on Androgen
Marcela Riveros Angel1, David Loeffler1, Ahmad Charifa1
1Department of Pathology & Laboratory Medicine, Oregon Health & Science University, Portland, Oregon.
Context:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry is facilitated by transmembrane protease serine 2 (TMPRSS2), which is regulated by the androgen receptor (AR). Androgen deprivation therapy (ADT), widely used in prostate cancer treatment, may potentially modulate TMPRSS2 expression, affecting SARS-CoV-2 infection susceptibility and severity.
Objective:
To evaluate the impact of ADT on pulmonary TMPRSS2 expression in prostate cancer patients and analyze differences in expression patterns associated with specific ADT regimens.
Design:
We examined TMPRSS2 immunohistochemical expression in lung tissue from 20 consecutive autopsy cases of men with prostate cancer (6 receiving ADT at time of death), compared with non-ADT prostate cancer patients and age-matched women controls. Histoscores were calculated by assessing percentage and intensity of pneumocyte TMPRSS2 expression.
Results:
Prostate cancer patients receiving ADT showed significantly reduced pulmonary TMPRSS2 expression compared to non-ADT patients (mean histoscores: 152.7 vs. 225.0, p=0.037) and age-matched women controls (mean histoscores: 152.7 vs. 238.0, p=0.024). Direct AR antagonists (apalutamide, bicalutamide) produced more pronounced TMPRSS2 suppression than GnRH modulators or androgen biosynthesis inhibitors. No significant correlation was observed between TMPRSS2 expression and Gleason score, PSA levels, or underlying lung pathology.
Conclusion:
Our findings demonstrate that ADT significantly reduces pulmonary TMPRSS2 expression, with direct AR antagonists showing the strongest effect. This suggests a potential mechanistic explanation for differential COVID-19 susceptibility and provides rationale for investigating AR-targeted therapies as potential protective interventions against SARS-CoV-2 infection severity.
Insights
Androgen deprivation therapy (ADT) significantly lowers pulmonary TMPRSS2 expression in prostate cancer patients, particularly with direct AR antagonists. This finding offers insights into COVID-19 susceptibility and potential therapeutic strategies.
Area of Science:
- Oncology
- Virology
- Pulmonology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses transmembrane protease serine 2 (TMPRSS2) for cellular entry.
- TMPRSS2 expression is regulated by the androgen receptor (AR).
- Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer and may influence TMPRSS2 levels.
Purpose of the Study:
- To investigate the effect of ADT on pulmonary TMPRSS2 expression in prostate cancer patients.
- To compare TMPRSS2 expression across different ADT regimens.
Main Methods:
- Immunohistochemical analysis of TMPRSS2 expression in lung tissue from prostate cancer patients (ADT and non-ADT groups) and age-matched female controls.
- Histoscores were calculated based on the percentage and intensity of pneumocyte TMPRSS2 expression.
Main Results:
- ADT significantly reduced pulmonary TMPRSS2 expression compared to non-ADT patients and controls (p<0.05).
- Direct AR antagonists (apalutamide, bicalutamide) demonstrated the most significant TMPRSS2 suppression.
- No correlation was found between TMPRSS2 expression and Gleason score, PSA levels, or lung pathology.
Conclusions:
- ADT effectively downregulates pulmonary TMPRSS2 expression, with direct AR antagonists showing the strongest effect.
- This modulation of TMPRSS2 may explain differential COVID-19 susceptibility in patients undergoing ADT.
- AR-targeted therapies warrant investigation as potential interventions to mitigate SARS-CoV-2 infection severity.
