Immunohistochemistry as an adjunct in the differential diagnosis of radiation-induced atypia versus urothelial carcinoma in situ of the bladder: a study of 45 cases

Hum Pathol. 2013 May;44(5):860-6. doi: 10.1016/j.humpath.2012.08.011. Epub 2012 Nov 27.


Muscle invasive urothelial carcinoma has been treated with cystectomy ± adjuvant therapy. Recently, a bladder-sparing protocol has been offered to selected patients closely followed with surveillance biopsies. In this setting, radiation-induced changes (RAD-Ch) may be very difficult to distinguish from carcinoma in situ, and failing to recognize them may lead to overtreatment. We ascertained the role of immunohistochemistry using cytokeratin (CK) 20, p53, and CD44s in bladder biopsies from 28 patients with a history of bladder radiation and 17 with carcinoma in situ without radiation. Negative or weak multifocal nuclear p53 staining was seen in 24 of 28 RAD-Ch cases, whereas strong and diffuse nuclear p53 staining was found in 8 of 17 carcinoma in situ cases and moderate and focal to multifocal in 3. CK20 showed strong cytoplasmic staining of only umbrella cells in 22 of 28 RAD-Ch cases. In contrast, 11 of 17 carcinomas in situ showed diffuse and strong CK20 positivity and 5 moderate and focal to multifocal positivity. All carcinomas in situ with weak or no p53 showed significant CK20 staining except 1. CD44s displayed diffuse membranous positivity in 7 of 17 RAD-Ch cases and up to mid-third in 8. Only 1 of 17 carcinomas in situ had diffuse membranous CD44s staining. Diffuse and significant CK20 expression was seen in most carcinomas in situ. Strong and diffuse p53 expression was only seen in carcinoma in situ (~50%), whereas diffuse CD44s staining was typically only seen in RAD-Ch. Our data suggest that a CK20(-) p53(-) CD44a panel proves to be very helpful (CK20 more reliable than p53 or CD44s) in the diagnosis of RAD-Ch.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma in Situ / diagnosis*
  • Carcinoma in Situ / pathology
  • Carcinoma, Transitional Cell / diagnosis*
  • Carcinoma, Transitional Cell / pathology
  • Diagnosis, Differential
  • Humans
  • Hyaluronan Receptors / metabolism
  • Immunohistochemistry
  • Keratin-20 / metabolism
  • Neoplasms, Radiation-Induced / diagnosis*
  • Tumor Suppressor Protein p53 / metabolism
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology
  • Urothelium / pathology


  • Biomarkers, Tumor
  • CD44S antigen
  • Hyaluronan Receptors
  • Keratin-20
  • Tumor Suppressor Protein p53