Researchers evaluated immunohistochemical (IHC) classification of muscle-invasive bladder cancer and the association with programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression in a retrospective cross-sectional study. Muscle-invasive bladder cancer accounts for about one third of bladder cancers and is associated with high metastatic potential. While transcriptomic profiling has been used for molecular classification, IHC provides a cost-effective approach that can be applied in routine pathology.
The analysis, published in Diagnostic Pathology, included 124 patients treated between 2020 and 2023 with transurethral resection or radical cystectomy for urothelial carcinoma at a single institution in Iran. Tumors were classified with GATA3, CK5/6, and p16 markers into luminal, basal, or other groups. Luminal tumors were subclassified as luminal unstable (LumU; GATA3+, CK5/6–, p16+) or luminal papillary (LumP; GATA3+, CK5/6–, p16–). Clinicopathologic features and expression of PD-1 and PD-L1 were assessed.
Of all cases, 63.8 percent were luminal, 24.8 percent basal, and the remainder other. Among luminal cases, 36.2 percent were LumU and 27.6 precent LumP. Basal tumors were more often stage III compared with luminal tumors (p < 0.05). PD-1 expression, at a 1 percent cut-off, was present in 70.5 percent of tumors, with the highest frequency in LumU (84.2 percent) and LumP (79.3 percent). PD-1 expression was significantly higher in luminal compared with basal tumors (82.1 percent vs 53.8 percent, p < 0.01). PD-L1 expression, at a 1 percent cut-off, was observed in 40 percent of tumors and was significantly associated with stage III disease (p < 0.05). PD-L1 was more frequently expressed in basal compared with luminal tumors (57.7 percent vs 34.3 percent, p < 0.05).
The results indicate that IHC classification with a limited marker panel can stratify MIBC into luminal, basal, and other subtypes, with further subdivision of luminal tumors by p16 status. Differences in PD-1 and PD-L1 expression were identified between subtypes and by tumor stage. The study did not assess survival outcomes.
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