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

Abstract

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.

Molecular profile of pure squamous cell carcinoma of the bladder identifies major roles for OSMR and YAP signalling

“…As reported previously in bladder SCC [16,85], the basal/squamous subtype of MIBC [86], and in UC with SD [87,88], we found upregulated expression of PD-L1 (CD274) and confirmed a previous finding of amplification of the gene [66] in some pure SCC. We also confirm upregulated expression of EGFR in these and SD tumours [89,90].…”

Programmed Cell Death-Ligand-1 expression in Bladder Schistosomal Squamous Cell Carcinoma – There’s room for Immune Checkpoint Blockage?

“…In the IHC staining the authors used three clinically available antibodies. The positivity score varied accordingly histological subtype being higher in pSCC ( 73 ). These conclusions agree with a study performed by Lee et al.…”

Squamous Cell Carcinoma of Bladder

“…Risk factors associated with the development of squamous cell include chronic or recurrent urinary tract infections (UTIs), bladder stones, pelvic radiotherapy (RT), previous intravesical Bacillus Calmette-Guerin (BCG) therapy, and prolonged cyclophosphamide treatment, especially when complicated by hemorrhagic cystitis, in addition to schistosome infection [3]. Although smoking raises the risk of squamous cell carcinoma [21,22], an observational study with long-term follow-up reveals that patients with pure squamous cell carcinoma are more likely to be female and have never smoked than patients with urothelial carcinoma [23]. In some studies, chronic indwelling catheters have also been associated with an increased risk of squamous cell carcinoma, while the relationship is controversial.…”

“…Limited data suggest that squamous cell carcinoma tends to be locally advanced or worse at diagnosis and relatively resistant to chemotherapies used for metastatic urothelial carcinoma [23,[39][40][41]. We prefer that these patients participate in a prospective clinical trial in view of these results.…”