Expression of TOMM34 and Its Clinicopathological Correlations in Urothelial Carcinoma of the Bladder

Pathol Oncol Res. 2020 Jan;26(1):411-418. doi: 10.1007/s12253-018-0524-3. Epub 2018 Oct 31.

Abstract

The substantial difference between normal cells and cancer cells in terms of their energy metabolism in mitochondria provides an interesting basis for the development of novel therapeutic agents targeting energy machinery of tumour cells. TOMM34 is one of the Tom (translocase of the outer membrane of mitochondria) family that was found to be overexpressed in colorectal, hepatocellular, lung and early invasive breast carcinomas. The expression profile of mitochondrial translocases in bladder cancer compared to normal urinary bladder tissues has not been investigated yet. Therefore, the aim of the current study is to investigate the expression pattern of TOMM34 in bladder cancer tissues and explore its correlation with the clinico-pathological parameters of those cases. Sixty patients who underwent either transurethral resection or radical cystectomy for bladder cancer were included in this study with revision of all their clinicopathological data and tumor slides. Ten histologically normal urothelial biopsies were also included. Immunohistochemical staining for TOMM34 was done and semi-quantitatively scored using the modified H-score. All relations were analysed using established statistical methodologies. TOMM34 overexpression was significantly associated with high tumour stage, muscle invasion and high grade. Significant positive association was observed between TOMM34 expression and poor outcome in terms of shorter disease-specific survival. This study suggests TOMM34 as a biomarker of progression and poor prognosis in urothelial cell carcinoma patients. Furthermore, we suggest a role played by mitochondrial machinery in urothelial cell carcinoma progression, which is a potential target for the newly-discovered vaccine therapy for urothelial cell carcinoma.

Keywords: Markers; Mitochondrial; TOMM34; Urothelial.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Membrane Transport Proteins / biosynthesis*
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Prognosis
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • TOMM34 protein, human