Loss of glutamine synthetase expression may support a diagnosis of urothelial carcinoma in situ


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Öz M., Ertunç O., Öğüt B., Tuna E. B., Işık Gönül İ.

37th European Congress of Pathology, Vienna, Austria, 6 - 10 September 2025, vol.487, pp.559-560, (Summary Text)

  • Publication Type: Conference Paper / Summary Text
  • Volume: 487
  • City: Vienna
  • Country: Austria
  • Page Numbers: pp.559-560
  • Gazi University Affiliated: Yes

Abstract

Background & Objectives: Glutamine synthetase (GS) is a critical enzyme that is responsible for the synthesis of glutamine from glutamate and ammonia and hence is involved in glutamine metabolism. Glutamine plays an important role in maintaining the function of many cells as a nucleotide and a main source of energy for rapidly dividing cells. The aim of this study was to investigate the immunohistochemical expression of GS in the flat urothelial lesions of the bladder posing a diagnostic challenge (Urothelial carcinoma in situ? /Non-tumoral urothelium?)

Methods: This study included 50 patients diagnosed with urothelial carcinoma in situ (UCAIS) between 2022 and 2025 in our department. Paraffin blocks containing UCAIS areas with surrounding nonneoplastic urothelium were selected from the H&E-stained sections of the patients. Immunohistochemical staining was performed with GS antibody. The presence or absence of cytoplasmic expression in UCAIS and non-neoplastic urothelium were noted and results were statistically compared.

Results: 6 cases were excluded from the study because of sub-optimal staining results. Non-tumoral epithelium was not observed in the immunohistochemically stained sections of 18 patients. However, GS was not expressed in the UCAIS areas in these cases. In the remaining 26 cases, which included both UCAIS and non-tumoral urothelium, we observed that GS expression was maintained in nontumoral urothelial areas, however it was lost in UCAIS areas. This difference was statistically significant (p<0.001).

Conclusion: To the best of our knowledge, this is the first study to evaluate GS expression in urothelial tumours, in which we showed that GS expression is maintained in non-tumoral urothelium, however its expression is lost in UCAISs. This difference may aid in the differential diagnosis of UCAIS in routine pathology work up. However, the molecular mechanisms underlying GS homeostasis and glutamine metabolism in UCAIS and other urothelial tumours need further effort to be discovered in the future.