BCL-2 and γ-H2AX immunostaining profile in urothelial bladder cancer prognosis

Pathol Res Pract. 2024 Dec:264:155680. doi: 10.1016/j.prp.2024.155680. Epub 2024 Oct 26.

Abstract

Urothelial bladder carcinoma (UBC) is a malignant neoplasm of the urinary tract that is highly prevalent worldwide and has a high rate of tumor recurrence. It is known that the BCL2 apoptosis regulator (BCL-2) gene encodes a mitochondrial protein that regulates programmed death cells by apoptosis. In contrast, the H2A.X histone variant (H2AX) gene encodes a histone responsible for regulating and signaling genomic instability processes. The present study aimed to analyze the immunostaining profiles of BCL-2 and γ-H2AX proteins in tissue samples (n=80) from UBC patients (muscle-invasive MI; and non-muscle invasive NMI) using indirect immunohistochemistry and to correlate the results with prognostic and clinical parameters. BCL-2 protein expression was cytoplasmic and absent in half of the samples, including the MI and NMI groups. Strong nuclear expression was observed for γ-H2AX, predominant in the MI samples. The immunostaining profile of both proteins was not associated with tumor recurrence or invasion, and no significant associations were found in relation to prognosis (tumor grade, pathological staging). No significant correlation was found between protein profiles in malignant tissue. All in all, BCL-2 and γ-H2AX did not prove to be candidate markers for UBC clinical management in the present sample, despite their expression in malignant bladder tissue.

Keywords: apoptosis; genomic instability; muscle invasion; protein expression; tumor recurrence.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / pathology
  • Female
  • Histones* / metabolism
  • Humans
  • Immunohistochemistry*
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2* / analysis
  • Proto-Oncogene Proteins c-bcl-2* / metabolism
  • Urinary Bladder Neoplasms* / metabolism
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Histones
  • Proto-Oncogene Proteins c-bcl-2
  • Biomarkers, Tumor
  • H2AX protein, human
  • BCL2 protein, human