The Significance of Squamous Histology on Clinical Outcomes and PD-L1 Expression in Bladder Cancer

Jennifer B. Gordetsky, Kathleen W. Montgomery, Giovanna A. Giannico, Soroush Rais-Bahrami, Prabin Thapa, Stephen Boorjian, Igor Frank, John Cheville

Research output: Contribution to journalArticlepeer-review


Objectives. To compare the clinicopathologic characteristics of urothelial carcinoma (UC), urothelial carcinoma with squamous differentiation (UCSD), and squamous cell carcinoma (SCC) of the bladder, which have been suggested to differ in terms of risk factors, immunophenotype, and prognosis. Methods. We evaluated the clinicopathologic features of radical cystectomy specimens between 1980 and 2015 with a diagnosis of SCC, UCSD, and UC. PD-L1 immunohistochemistry (clinically available clones 22C3, SP142, and SP263) was performed on SCC and UCSD. Multivariate Cox regression was used to identify prognostic factors. Kaplan–Meier curves were plotted to assess cancer-specific survival (CSS). Results. Of the 1478 cases, there were 1126 UC (76%), 217 UCSD (15%), and 135 SCC (9%). Bladder cancer was more common in men than women (80% vs 20%, P <.0001). However, a higher proportion of SCC and UCSD occurred in women (SCC-36%, UCSD-22%, UC-18%). Women were significantly more likely to be never smokers in all 3 cohorts (UC: 45% vs 16%, UCSD: 44% vs 12%, SCC: 40% vs 18%, P <.0001). Patients with SCC and UCSD were at a higher pathologic stage (>pT2) at the time of cystectomy (UCSD-74%, SCC 71%, UC-44%, P <.0001) and had worse CSS compared to patients with UC (P = 0.006). SCC had higher PD-L1 scores (all clones) than UCSD (P <.0001). PD-L1 22C3 (P =.02, HR: 0.36) and SP142 scores (P =.046, HR: 0.27) predicted CSS on Kaplan–Meier analysis for SCC cases. Conclusions. UC, UCSD, and SCC are associated with different risk factors, gender distributions, and clinical outcomes. PD-L1 is expressed in SCC and UCSD, suggesting some patients may benefit from targeted therapy.

Original languageEnglish (US)
Pages (from-to)6-14
Number of pages9
JournalInternational Journal of Surgical Pathology
Issue number1
StatePublished - Feb 2022


  • PD-L1
  • pathology
  • squamous cell carcinoma
  • survival
  • urinary bladder
  • urothelial carcinoma

ASJC Scopus subject areas

  • Surgery
  • Anatomy
  • Pathology and Forensic Medicine


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