Tumor Budding Is an Independent Prognostic Factor in Pancreatic Adenocarcinoma and It Positively Correlates with PD-L1 Expression on Tumor Cells

Abstract

Pancreatic adenocarcinoma is one of the leading causes of cancer-related death in developed countries. Only 15% of patients are candidates for radical surgery, and adequate prognostication may guide proper postsurgical management. We aimed to retrospectively assess the prognostic significance of the immunohistochemical expression of immune checkpoint receptors (PD-L1 and VISTA), markers of systemic inflammation, thrombosis in the tumor area, and the tumor budding in the group of 107 patients diagnosed with pancreatic adenocarcinoma in a single center. The high expression of PD-L1 on tumor cells (TCs) was associated with worse overall survival (OS, p = 0.041, log-rank). On the contrary, high PD-L1 or VISTA on tumor-associated immune cells (TAICs) was correlated with better OS (p = 0.006 and p = 0.008, respectively, log-rank). The joint status of PD-L1 on TCs and TAICs stratified patients into three prognostic groups. The cases with high-grade budding were characterized by higher PD-L1 expression on TCs (p = 0.008) and elevated systemic inflammatory markers. Moreover, budding was identified as the independent prognostic factor in multivariate Cox regression analysis (HR = 2.87; 95% CI = 1.75–4.68; p < 0.001). To conclude, the pattern of PD-L1 and VISTA expression was associated with survival in univariate analysis. Tumor budding accurately predicts outcomes in pancreatic cancer and should be incorporated into routine histopathological practice.

Prognostic significance of tumour budding in noncolorectal gastrointestinal tract and pancreatobiliary tract: a systematic review and meta‐analysis

“…Subsequently, a full‐text review was performed, during which studies with inadequate data or cohort presentation, as well as those lacking full‐text availability, the inadequate study design was excluded. Ultimately, 57 studies met our inclusion criteria and were included in our systematic review and meta‐analysis 4,5,16–70 . Manual‐checking references to ensure comprehensives did not yield any additional studies.…”

Unraveling the potential of CD8, CD68, and VISTA as diagnostic and prognostic markers in patients with pancreatic ductal adenocarcinoma

“…reported that although VISTA expression in immune cells and endothelial cells did not show an association with patient survival, there was a significant correlation between high levels of VISTA expression in pancreatic tumor cells and improved overall survival (OS) ( 78 ). Better OS is associated with high expression of PD-L1 or VISTA on immune cells present in the TME of PDAC ( 91 ). In contrast, in a study by Blando et al., survival was found to have an inverse correlation with the expression of the VISTA gene ( 30 ).…”