The emerging role of cell cycle protein p53 expression by tumor cells and M2-macrophage infiltration in urinary bladder cancer

Urol Oncol. 2023 Mar;41(3):148.e9-148.e16. doi: 10.1016/j.urolonc.2022.12.005. Epub 2023 Jan 24.

Abstract

Purpose: To investigate the association between p53 expression in tumor cells and intratumoral macrophage infiltration in muscle-invasive urinary bladder cancer (MIBC) in relation to clinical and pathological variables and outcomes after radical cystectomy.

Methods: Tumor specimens of the primary tumor from patients treated with radical cystectomy for MIBC were immunostained with the M2-macrophage-specific marker CD163 and the cell cycle protein p53. The expression of these markers was analyzed in relation to patients´ and tumor characteristics and outcome.

Results: Out of 100 patients with urinary bladder cancer (UBC) pathological stage T1-4 N0-3 M0, 77% were men. The patients had a median age of 69 years and 80% had nonorgan-confined tumors (pT3-4). Lymph node metastasis was found in 42 (42%) of all patients. P53-positive expressions were found in 63 (63%) patients. Strong macrophage infiltration in the tumor microenvironment was shown in 74 (74%) patients. Combinations of CD163/p53 status were as follows: CD163+/p53+, 50%; CD163+/p53-, 24%; CD163-/p53+, 13%; and CD163-/p53-, 13%. Patients with CD163+/P53+ had higher proportions of organ-confined tumors.

Conclusions: In the present series of patients with MIBC treated with cystectomy, we found that high CD163+ macrophage infiltration in the tumor micro-environment often was combined with p53+ cancer cells. This simultaneous expression of p53 by tumor cells and increased infiltration of M2-macrophages in the tumor microenvironment was associated with improved CSS, which might indicate a possible protective effect of M2 macrophages in p53+ tumors. Further investigations are needed to explore the biological relation between mutational burden and immune profile in MIBC.

Keywords: Macrophage; Urinary bladder cancer; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Cycle Proteins / metabolism
  • Cystectomy
  • Female
  • Humans
  • Macrophages
  • Male
  • Tumor Microenvironment
  • Tumor Suppressor Protein p53* / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Tumor Suppressor Protein p53
  • Cell Cycle Proteins