Could double stain for p53/CK20 be a useful diagnostic tool for the appropriate classification of flat urothelial lesions?

Pathol Res Pract. 2022 Jun:234:153937. doi: 10.1016/j.prp.2022.153937. Epub 2022 May 6.

Abstract

Background: The differential diagnosis between flat urothelial lesions [reactive urothelial atypia (RUA), atypia of unknown significance (AUS), urothelial dysplasia (UD) and carcinoma in situ (CIS)] has relevant prognostic and therapeutic implications. This crucial distinction could be very challenging but it is currently performed on hematoxylin and eosin (H&E) slides, with a great amount of partially discordant and/or not conclusive findings of the potential adjunctive role of immunohistochemistry. Herein, we tested double staining (DS) for p53/CK20 to verify if p53(+) cells, CK20(+) cells and double-positive cells (DPCs) are differentially expressed among these lesions and if p53/CK20 could be a useful tool in this diagnostic setting.

Methods: We tested 50, 9, 36 and 29 consecutive and retrospectively enrolled cases of RUA, AUS, UD and CIS, respectively. p53(+) cells, CK20(+) cells and DPCs were evaluated and compared by adopting the appropriate statistic tests (Mann-Whitney U and Kruskal-Wallis tests).

Results: We found that p53(+) cells (p = 0.000), CK20(+) cells (p = 0.000) and DPCs (p = 0.000) showed statistically significant differences among the different flat urothelial lesions. Besides, when dichotomized, both CIS and RUA are easily differentiable from their histological mimickers adopting all these markers; by contrast, AUS and UD did not reach statistically significant differences able to differentiate them from each other [p53(+) cells, p = 0.123; CK20(+) cells, p = 0.567; DPCs, p = 0.409], except if compared to CIS [AUS VS CIS: p53(+) cells, p = 0.013; CK20(+) cells, p = 0.000; DPCs, p = 0.000; UD vs CIS: p53(+) cells, p = 0.000; CK20(+) cells, p = 0.000; DPCs, p = 0.000].

Conclusions: p53(+) cells, CK20(+) cells and DPCs are differently expressed by flat urothelial lesions and p53/CK20 could be a time- and money-saving tool for the appropriate management of these lesions if applied to a routine scenario.

Keywords: Carcinoma in situ; Double stain; Flat urothelial lesions; Urothelial dysplasia; WHO.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Carcinoma in Situ* / diagnosis
  • Carcinoma in Situ* / metabolism
  • Carcinoma in Situ* / pathology
  • Carcinoma, Transitional Cell* / diagnosis
  • Carcinoma, Transitional Cell* / metabolism
  • Carcinoma, Transitional Cell* / pathology
  • Coloring Agents
  • Humans
  • Keratin-20 / analysis
  • Keratin-20 / metabolism
  • Retrospective Studies
  • Staining and Labeling
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism
  • Urinary Bladder Neoplasms* / diagnosis
  • Urinary Bladder Neoplasms* / metabolism
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Biomarkers, Tumor
  • Coloring Agents
  • KRT20 protein, human
  • Keratin-20
  • TP53 protein, human
  • Tumor Suppressor Protein p53