Abstract 488P
Background
Gastric and oesophageal adenocarcinomas (GOCs) have a dismal prognosis. Tumour budding (TB) identified on resected GOCs are associated with poorer disease-free survival (DFS). E-cadherin is an epithelial marker, whilst urokinase plasminogen activator receptor (uPAR) is a known inducer of cancer cells to the mesenchymal phenotype. We aimed to assess the relationship between E-cadherin and uPAR expression levels on TBs and DFS of patients with resected GOCs.
Methods
111 patients completed curative intent surgery for GOC at the Illawarra Shoalhaven Local Health District, Australia, between 2013-2022. TB was assessed as per the international tumour budding cancer consensus guidelines; in brief, TBs are a cluster (up to 4) cells beyond the invasion zone of the tumour assessed by hotspot method at 20x magnification. Regions with highest TB assessment on Haematoxylin and Eosin (H&E) were analysed by uPAR and E-cadherin immunohistochemistry (IHC) on serial sections. High TB was classified as >5 TBs in the region of interest with either H&E or uPAR IHC. Strong E-cadherin were classified as strong IHC on all tumour cells. Mesenchymal phenotype tumours were classified as tumours with strong E-cadherin IHC and uPAR IHC expression on more than 5% of tumour cells, all other combinations were classified as epithelial phenotype. Survival analysis was performed using Kaplan-Meier and Cox Proportional Hazards methods.
Results
TB assessment was performed on 88 patients via H&E, and 61 patients using uPAR and E-cadherin IHCs. High H&E TBs was associated with shorter median DFS (37.8months Vs not reached [NR], HR 2.42 95%CI 1.04-5.66; p=0.03). High uPAR TBs was not significantly associated with DFS (30.6m for uPAR Vs NR; p=0.1). Strong E-cadherin expression on TB was associated with an improved DFS (20.2m V 43.9m, HR 0.41 95%CI 0.19-0.88, p=0.03). Mesenchymal phenotype TBs had the strongest association with DFS (12.6m Vs 43.9m; HR 3.20 95%CI 1.43-7.16, p=0.009), outperforming H&E, E-cadherin, or uPAR alone.
Conclusions
Our data confirms that mesenchymal phenotype TBs identifies GOC patients with poorest DFS, and that the combination of high uPAR/low E-cadherin expressing TBs represents a novel prognostic biomarker for poorer outcome in GOC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.