| Title: |
Fibroblast activation protein-α and the immune landscape : unraveling T1 non-muscle-invasive bladder cancer progression |
| Authors: |
Muilwijk, Tim; Baekelandt, Loic; Akand, Murat; Daelemans, Sofie; Marien, Koen; Waumans, Yannick; van Dam, Pieter-Jan; Kockx, Mark; Van den Broeck, Thomas; Van Cleynenbreugel, Ben; Van der Aa, Frank; Gevaert, Thomas; Joniau, Steven |
| Source: |
2666-1683 ; European urology open science |
| Publication Year: |
2024 |
| Collection: |
IRUA - Institutional Repository van de Universiteit Antwerpen |
| Subject Terms: |
Human medicine |
| Description: |
Background and objective: The tumor microenvironment (TME) in non-muscleinvasive bladder cancer (NMIBC) plays an important role in the anticancer response. We aimed to identify the prognostic biomarkers in the TME of patients with NMIBC for progression to >T2. Methods: From our institutional database, 40 patients with T1 high -risk NMIBC who progressed were pair matched for Club Urologico Espa & ntilde;ol de Tratamiento Oncologico (CUETO) progression variables with 80 patients who never progressed despite longer follow-up. Progression was defined as >T2 or extravesical disease. Patients were treated at least with bacillus Calmette-Gu & eacute;rin (BCG) induction (five or more of six doses). Immunohistochemical (IHC) markers for the TME were used on tissue at first T1 diagnosis: CD8-PanCK, GZMB-CD8-FOXP3, CD163, PD -L1 SP142/SP263, fibroblast activation protein-alpha (FAP), and CK5-GATA3. Full tissue slides were annotated digitally. Relative marker area (IHC-positive area/total area) or density (IHC-positive cells per area; n/mm2) was calculated, differentiating between regions of interest (ROIs; T1, Ta, and carcinoma in situ) and between compartments (stromal, epithelial, and combined). Differences in IHC variables were assessed using the t test, for continuous variables using analysis of variance and comparisons of more than two groups using Tukey's test. Conditional logistic regression for progression at 5-yr follow-up was performed with clusters based on pair matching. Key findings and limitations: Only FAP expression (increase per 50%) in T1 (odds ratio [OR]: 1.33; 95% confidence interval [CI]: 1.04-1.70) and all ROIs combined (OR: 1.62; 95% CI: 1.14-2.29) correlated significantly with progression. None of the other clinicopathological/IHC variables correlated with progression. Conclusions and clinical implications: FAP is a potential prognostic biomarker for progression in high -risk NMIBC. FAP is a marker for cancer -associated fibroblasts and is linked to immunosuppression and ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/isi/001263281300001 |
| Availability: |
https://hdl.handle.net/10067/2070190151162165141; https://repository.uantwerpen.be/docstore/d:irua:24485 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.E8F7F14F |
| Database: |
BASE |