Investigating Intensity and Percentage of p53 Nuclear Expression in Prostate Cancer: Findings from a Cohort of U.S. Military Veterans
by
, , , , and
William R. Gesztes
1,2,3,*
,
Coen J. Lap
4,5,
Rithika Rajendran
1,
Maryam M. Dalivand
1,2,
Guoqing Diao
6,
Shanshan Liu
6,
Maneesh Jain
4 and
Victor E. Nava
1,2
1
Department of Pathology, Washington DC VA Medical Center, Washington, DC 20422, USA
2
Department of Pathology, The George Washington University Hospital, Washington, DC 20037, USA
3
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
4
The Edward P. Evans Precision Oncology Center of Excellence, Washington DC VA Medical Center, Washington, DC 20422, USA
5
Department of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA
6
Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20037, USA
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(6), 1004; https://doi.org/10.3390/cancers17061004
Submission received: 3 February 2025
/
Revised: 11 March 2025
/
Accepted: 14 March 2025
/
Published: 17 March 2025
(This article belongs to the Section Cancer Pathophysiology)
Simple Summary
The role of p53 immunohistochemistry (IHC) in predicting disease progression in prostate cancer (PCa) was investigated, revealing an unmet need to better understand the interpretation of p53 nuclear expression. This study was conducted at the DC VA Medical Center and involved 84 patients (majority self-identified as African American) with PCa diagnosed between 1996 and 2021. Nuclear expression of p53 was scored in various specimens according to the intensity (0, 1+, 2+, 3+) and percentage (0%, <1%, 1–5%, >5%) of p53-positive tumor cells. In total, 40% of patients were found to have p53 expression, with 21% showing maximum intensity (3+). Maximum intensity was significantly associated with a higher Grade Group (p < 0.001), elevated PSA levels at the time of biopsy (p < 0.001), biochemical recurrence (p < 0.001), and metastasis (p < 0.001). Notably, only patients who developed metastatic disease were found to have maximum p53 intensity. This study underscores the importance of evaluating p53 nuclear intensity, in addition to percentage p53 positivity, to predict disease progression in PCa.
Abstract
Background: Next-generation sequencing has revealed TP53 alterations in localized prostate cancer (PCa), suggesting growing clinical potential for p53 immunohistochemistry (IHC). Prior research supports the use of IHC for the detection of p53 overexpression to predict the presence of TP53 alterations known to be associated with adverse outcomes. However, to reach a consensus definition of p53 overexpression in PCa, further insights are needed. This study aimed to compare two fundamental approaches of evaluating p53 expression across a variety of specimens regarding PCa progression. Methods: This study included 84 patients (75% self-identified as African American) diagnosed with PCa between 1996 and 2021 at the DC VA Medical Center. Representative sections of core biopsies, radical prostatectomies, transurethral prostate resections, and metastatic deposits were examined. p53 nuclear expression was scored according to the highest intensity observed (0, 1+, 2+, 3+) and the percentage (0%, <1%, 1–5%, >5%) of tumor cells expressing any level of intensity in the aggregate tumor area. All slides were reviewed by two independent pathologists. Pertinent clinical data were collected. Results: A total of 34 patients (40%) exhibited p53 nuclear expression, of which 18 (21%) showed the maximum (3+) intensity. The presence of maximum intensity, regardless of percentage, was found to be associated with Grade Group (p < 0.001), higher PSA at biopsy (p < 0.001), BCR (p < 0.001) and metastasis (p < 0.001). Importantly, maximum p53 intensity was identified only in patients who developed metastatic disease. Conclusions: Maximum (3+) p53 nuclear intensity of any percentage is highly associated with disease progression in PCa, suggesting that optimal determination of p53 overexpression should incorporate intensity.
Keywords:
prostate cancer; p53; TP53; biomarker; immunohistochemistry; African American; progression
