Prognostic significance of tumour budding, tumour-stroma ratio and desmoplastic stromal reaction in gall bladder carcinoma

Aims and methods The prognostic role of tumour budding (TBd) and its interaction with the stromal microenvironment has gained a lot of attention recently, but remains unexplored in gall bladder cancer (GBC). We aimed to study the interrelationship of TBd by International Tumour Budding Consensus Conference scoring system, tumour-stroma ratio (TSR) and desmoplastic stromal reaction (DSR) with the conventional clinicopathological prognostic factors, mortality and overall survival (OS) in 96 patients of operated GBC. Results Higher age, high TNM stage, lymphovascular and perineural invasion, positive resection margins, higher TBd score, low TSR and immature DSR were significantly associated with worse OS. However, on multivariate analysis, only metastases, positive resection margins and TSR <50% proved to be independent prognostic factors. The TBd score of stroma-rich tumour group (6.40 +/- 4.69) was significantly higher than that of stroma-poor group (2.77 +/- 3.79, p <= 0.001). The TBd score of immature and intermediate DSR groups was significantly higher than that of mature group (p <= 0.001 and p=0.002, respectively). There was a strong interobserver agreement for TBd score, TSR and type of DSR (Cohen's Kappa=0.726 to 0.864, p <= 0.001). Stroma-rich tumours were significantly associated with immature DSR and fibrotic DSR with high TSR (p <= 0.001). Conclusion A high TBd, low TSR and immature DSR were significantly associated with several high-risk clinicopathological parameters and poor OS in GBC. These novel, simple, reproducible and cost-effective parameters may be included in the routine reporting checklist for GBC as additional prognostic parameters that can substratify the high-risk patients.