Abstract
Background: bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expression of miRNA-145 and miRNA-200a, FGFR3 gene expression, and mutation status in tissue specimens of the luminal subtype of newly diagnosed high and low grade NMIBC. Methods: twenty patients with primary luminal NMIBC were enrolled in the study. Tumor grade and risk level were determined in accordance with European Organization for Research and Treatment of Cancer (EORTC) guidelines and World Health Organization (WHO) classification. Neoplasm molecular subtype and PD-L1 expression level were assessed by immunohistochemistry. We used real-time PCR to evaluate the expression of microRNAs and FGFR3. We detected FGFR3 hotspot mutations in codons 248 and 249 by Sanger sequencing. Results: high grade primary luminal NMIBC showed comparatively higher expression of PD-L1 and microRNA-145 than a low grade tumor, whereas the latter had a higher FGFR3 expression and hotspot mutation rate. The tumor grade (HR = 571.72 [11.03–2.96] p = 0.002), PD-L1 expression (HR = 2.33 [0.92–1.92] p = 0.012), and FGFR3 expression (HR = 0.08 [0.17–0.42] p = 0.003) were associated with relapse-free survival. Conclusions: tumor grade in association with PD-L1 and FGFR3 expression can be considered as a complex predictor for primary luminal NMIBC progression.
Highlights
Bladder cancer remains to be one of the most common human genitourinary tumors worldwide with high cost per patient and high mortality rate [1,2]
We investigated here the prognostic roles of microRNA-200a, microRNA-145, FGFR3 expression, and mutation status in association with PD-L1 expression in patients with primary luminal non-muscular invasive bladder carcinoma (NMIBC)
The proportion of cancer cells positively stained for the PD-L1 membrane expression was statistically higher in GATA3-positive high grade primary NMIBCs (n = 8) than in low grade bladder carcinomas (n = 12), with average values of 26.8% vs. 16.3%, respectively (p = 0.017)
Summary
Bladder cancer remains to be one of the most common human genitourinary tumors worldwide with high cost per patient and high mortality rate [1,2]. The first one at the time of diagnosis was proven to be less aggressive than the latter [3,4], but treatment of both requires stringent interventional and surveillance protocols [5]. Biological and genetic heterogeneity of NMIBC serves as a basis for the disease molecular classification. According to the tumor molecular profiling made by Dadhania and colleagues, CR5/6 and GATA3 expression levels are currently used to designate NMIBC into basal, luminal, and double-negative subtypes [6]. Identification of the pivotal role of immune checkpoint molecules has drastically changed diagnostic, prognostic, and treatment approaches to many malignancies including bladder cancer [7,8,9]
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