Increased PD-L1 expression in high-grade bladder cancer with squamous cell differentiation in Bulgarian and French patients' samples

Gulinac, Milena; Dikov, Dorian; Velikova, Tsvetelina; Belovezhdov, Veselin

doi:10.1016/j.anndiagpath.2020.151640

Cited by 4 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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].…”

Section: Discussionsupporting

confidence: 92%

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

Hurst

Guo

Platt

et al. 2022

The Journal of Pathology CR

View full text Add to dashboard Cite

Pure squamous cell carcinoma (SCC) is the most common pure variant form of bladder cancer, found in 2-5% of cases. It often presents late and is unresponsive to cisplatin-based chemotherapy. The molecular features of these tumours have not been elucidated in detail. We carried out whole-exome sequencing (WES), copy number, and transcriptome analysis of bladder SCC. Muscle-invasive bladder cancer (MIBC) samples with no evidence of squamous differentiation (non-SD) were used for comparison. To assess commonality of features with urothelial carcinoma with SD, we examined data from SD samples in The Cancer Genome Atlas (TCGA) study of MIBC. TP53 was the most commonly mutated gene in SCC (64%) followed by FAT1 (45%). Copy number analysis revealed complex changes in SCC, many differing from those in samples with SD. Gain of 5p and 7p was the most common feature, and focal regions on 5p included OSMR and RICTOR. In addition to 9p deletions, we found some samples with focal gain of 9p24 containing CD274 (PD-L1). Loss of 4q35 containing FAT1 was found in many samples such that all but one sample analysed by WES had FAT1 mutation or deletion. Expression features included upregulation of oncostatin M receptor (OSMR), metalloproteinases, metallothioneins, keratinisation genes, extracellular matrix components, inflammatory response genes, stem cell markers, and immune response modulators. Exploration of differentially expressed transcription factors identified BNC1 and TFAP2A, a gene repressed by PPARG, as the most upregulated factors. Known urothelial differentiation factors were downregulated along with 72 Kruppel-associated (KRAB) domain-containing zinc finger family protein (KZFP) genes. Novel therapies are urgently needed for these tumours. In addition to upregulated expression of EGFR, which has been suggested as a therapeutic target in basal/squamous bladder cancer, we identified expression signatures that indicate upregulated OSMR and YAP/TAZ signalling. Preclinical evaluation of the effects of inhibition of these pathways alone or in combination is merited.

show abstract

Section: Discussionsupporting

confidence: 92%

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

Hurst

Guo

Platt

et al. 2022

The Journal of Pathology CR

View full text Add to dashboard Cite

show abstract

“…For accurate analysis, we reviewed a series of previous studies, based on PD-L1 assays (SP263) and cut-off values (TPS ≥ 25%) that were used in clinical trials of tislelizumab, and applied them to our case[ 18 , 25 ]. Furthermore, to minimize manual error, automated quantification and interpretation of the PD-L1 IHC results were adopted in this case.…”

Section: Discussionmentioning

confidence: 99%

Bladder preservation in complicated invasive urothelial carcinoma following treatment with cisplatin/gemcitabine plus tislelizumab: A case report

Yang¹,

Chen²,

Luo³

et al. 2023

World J Clin Cases

View full text Add to dashboard Cite

BACKGROUND Invasive urothelial carcinoma (UC) with squamous and glandular differentiation is a highly malignant and complicated pathological subtype, and the standard care is radical cystectomy (RC). However, urinary diversion after RC significantly reduces patient quality of life, thus bladder-sparing therapy has become a research hotspot in this field. Recently, five immune checkpoint inhibitors have been approved for systemic therapy of locally advanced or metastatic bladder cancer by the Food and Drug Administration, but the efficacy of immunotherapy combined with chemotherapy for invasive UC is still unknown, especially for pathological subtypes with squamous and glandular differentiation. CASE SUMMARY We report the case of a 60-year-old male who complained of repetitive painless gross hematuria and was diagnosed with muscle-invasive bladder cancer with squamous and glandular differentiation, defined as cT3N1M0 according to the American Joint Committee on Cancer, who had a strong desire to preserve the bladder. Immunohistochemical staining revealed that programmed cell death-ligand 1 (PD-L1) expression in the tumor was positive. Thus, a transurethral resection to maximize removal of the bladder tumor was performed under cystoscopy, and the patient subsequently received a combination of chemotherapy (cisplatin/gemcitabine) and immunotherapy (tislelizumab) treatment. No tumor recurrence in the bladder was observed following pathological and imaging examination after 2 cycles and 4 cycles of treatment, respectively. The patient achieved bladder preservation and has been tumor-free for more than two years. CONCLUSION This case shows that the combination of chemotherapy and immunotherapy might be an effective and safe treatment strategy for PD-L1 expression positive UC with divergent histologic differentiation.

show abstract

“…A French and Bulgarian cohort study also demonstrated that PD-L1 positive expression was associated with higher tumor grade and stage. A higher CPS in BUC with squamous differentiation ( 72 ). Other studies addressed the PD-L1 expression in pSCC, demonstrating that overall, pSCC presented a higher PD-L1 expression when compared with tumors with mixed histology.…”

Section: Pd-l1 Expression In Bladder Squamous Cell Carcinoma – ...mentioning

confidence: 99%

“…A French and Bulgarian cohort study also demonstrated that PD-L1 positive expression was associated with higher tumor grade and stage. A higher CPS in BUC with squamous differentiation (72). Other studies addressed the PD-L1 Recently, the expression of sPD-L1 as a prognosis marker was examined in the scope of BC and correlated with disease aggressiveness and ICB therapy outcomes (77,78).…”

Section: Pd-l1 Expression In Bladder Squamous Cell Carcinomaa Brief O...mentioning

confidence: 99%

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

Madureira

2022

Front. Immunol.

View full text Add to dashboard Cite

Schistosoma haematobium, the causative agent of urogenital schistosomiasis, is a carcinogen type 1 since 1994. It is strongly associated with bladder squamous-cell carcinoma in endemic regions, where it accounts for 53-69% of bladder-carcinoma cases. This histological subtype is associated with chronic inflammation being more aggressive and resistant to conventional chemo and radiotherapy. Immune-Checkpoint-Blockage (ICB) therapies targeting the Programmed-Cell-Death-Protein-1(PD-1)/Programmed-Cell-Death-Ligand-1(PD-L1) axis showed considerable success in treating advanced bladder urothelial carcinoma. PD-L1 is induced by inflammatory stimuli and expressed in immune and tumor cells. The binding of PD-L1 with PD-1 modulates immune response leading to T-cell exhaustion. PD-L1 presents in several isoforms and its expression is dynamic and can serve as its expression acts as a companion marker for patients’ eligibility, allowing the identification of positive tumors that are more likely to respond to ICB therapy. The high PD-L1 expression in bladder-urothelial-carcinoma and squamous-cell carcinoma may affect further ICB-therapy application and outcomes. In general, divergent histologies are ineligible for therapy. These treatments are expensive and prone to auto-immune side effects and resistance. Thus, biomarkers capable of predicting therapy response are needed. Also, the PD-L1 expression assessment still needs refinement. Studies focused on squamous cell differentiation associated with S. haematobium remain scarce. Furthermore, in low and middle-income-regions, where schistosomiasis is endemic, SCC biomarkers are needed. This mini-review provides an overview of the current literature regarding PD-L1 expression in bladder-squamous-cell-carcinoma and schistosomiasis. It aims to pinpoint future directions, controversies, challenges, and the importance of PD-L1 as a biomarker for diagnosis, disease aggressiveness, and ICB-therapy prognosis in bladder-schistosomal-squamous-cell carcinoma.

show abstract

Increased PD-L1 expression in high-grade bladder cancer with squamous cell differentiation in Bulgarian and French patients' samples

Cited by 4 publications

References 32 publications

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

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

Bladder preservation in complicated invasive urothelial carcinoma following treatment with cisplatin/gemcitabine plus tislelizumab: A case report

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

Contact Info

Product

Resources

About