The response to immune checkpoint inhibitors (ICIs) or enfortumab vedotin is limited in patients with upper urinary tract urothelial carcinoma (UTUC), and the development of new targeted therapy for UTUC is eagerly needed. Several biomarkers, including programmed cell death-ligand 1 (PD-L1), have already been reported as predictors of response to ICIs therapy for UTUC. Recently, several studies have shown that steroid hormone receptors, including the androgen receptor (AR), are associated with progression of urothelial carcinoma.
We prepared tissue microarrays (TMA) from paraffin blocks of UTUC specimens in 99 non-metastatic UTUC patients who underwent radical nephroureterectomy. With these TMA sections, we performed immunohistochemical staining for PD-L1 and AR and examined PD-L1 and AR expression levels in tumor cells. In addition, we analyzed the correlation between these markers and clinical prognosis in UTUC cases.
PD-L1 was positive in 24 (24%) of the 99 samples, whereas AR was positive in 20 (20%) patients. AR-negative samples had significantly higher PD-L1 expression level than that the AR-positive samples (mean value 4.70% versus 2.55%, p=0.0324). Among AR-positive cases, patients with absence of PD-L1 expression had significantly lower cancer-specific survival (CSS) than that in PD-L1 expression-positive cases (p=0.049), although PD-L1 expression had no significant impact on CSS in AR-negative cases (p=0.920).
Our findings suggest that AR is the promising target for UTUC treatment, especially in PD-L1-negative cases.
Cancer genomics & proteomics. 2024 Dec [Epub]
Yohei Okuda, Taigo Kato, Kazutoshi Fujita, Hiroaki Fushimi, Hiroshi Miyamoto, George J Netto, Norio Nonomura
Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan., Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan; ., Department of Urology, Kindai University Faculty of Medicine, Sayama, Japan., Department of Pathology, Osaka General Medical Center, Osaka, Japan., Departments of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, U.S.A., Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.