Expression of GLUT4 and FAP in urothelial bladder carcinoma: correlation with angiogenesis and clinicopathological characteristics

J Egypt Natl Canc Inst. 2022 Sep 26;34(1):40. doi: 10.1186/s43046-022-00145-0.


Background: Urothelial carcinoma (UC) is the most common type of bladder cancer. Glucose transporter 4 (GLUT4) is one of glucose transporter proteins' family which facilitates glucose transport inside the cells. It was found to be overexpressed in several malignant tumors. Cancer-associated fibroblasts (CAFs) are heterogeneous stromal cells located adjacent to cancer cells and are considered one of the most important tumor stromal cells. They have been associated with enhancing tumor growth and invasion. GLUT4 expression in malignant epithelial cells and fibroblast activation protein (FAP) expression in CAFs of UC in relation to angiogenesis and clinicopathological characteristics are studied in this work.

Materials and methods: The study was carried out on 72 paraffin blocks of UC (27 radical cystectomies and 45 transurethral resections). Immunohistochemical staining was performed with GLUT4, FAP, and CD34 antibodies. Expression of GLUT4 and FAP was classified according to the staining intensities and percentages into low and high groups. CD34-stained microvessels' mean count in five microscopic fields (×200) was taken as the microvessel density (MVD).

Results: GLUT4 overexpression was detected in 32 UC. It was significantly associated with high-grade tumors, advanced primary tumor (pT) stage, lymphovascular invasion (LVI), and regional lymph node invasion. High FAP expression was appreciated in 27 UC and was significantly linked to LVI and advanced TNM staging. Intratumor MVD significantly increased in UC with muscle invasion, LVI, and regional lymph node and/or distant metastasis. A significant positive correlation between GLUT4, FAP expression, and MVD was found.

Conclusion: GLUT4 and FAP expression was significantly associated with increased intratumor MVD and adverse clinicopathological factors.

Keywords: Angiogenesis; Clinicopathological characteristics; FAP; GLUT4; Immunohistochemistry; Urothelial carcinoma.

MeSH terms

  • Carcinoma, Transitional Cell* / metabolism
  • Glucose
  • Glucose Transport Proteins, Facilitative
  • Humans
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Paraffin
  • Urinary Bladder
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / metabolism


  • Glucose Transport Proteins, Facilitative
  • Paraffin
  • Glucose