Tumour Budding as an Independent Prognostic Factor for Survival in Patients With Distal Bile Duct Cancer

Background/Aim: Surgical resection is the standard treatment for bile duct cancer. However, even when surgical resection is possible, the 5-year survival rate is reportedly 25.05-5.0%. Therefore, bile duct cancer is associated with poor prognoses. We conducted a clinicopathological investigation, focusing on the histological phenomenon of tumour budding, which has previously been reported to be correlated with the survival of patients with a variety of cancers. Patients and Methods: To investigate the significance of tumour budding in distal bile duct cancer, we recruited 65 patients who underwent pancreatoduodenectomy at our institution between 1995 and 2011. Tumour budding was observed and evaluated using the `hot spot method'. The `low' budding group comprised 0-4 cell clusters and the `high' budding group >= 5 cell clusters. Additionally, immunostaining was performed in high-budding areas. Results: Tumour budding and stage were confirmed using a Cox proportional hazards model as independent prognostic factors for overall survival (p<0.05) in all patients. There was a significant association between budding and zinc finger E-box binding homeobox 1 expression, an endothelial-mesenchymal transition-induced transcription factor. In stage II cases, the prognosis was significantly worse in the 'high' budding group compared to that in the 'low' budding group. Conclusion: The budding phenomenon is an independent prognostic factor for patients with distal bile duct cancer. Understanding the mechanisms underlying tumour budding in distal bile duct cancer and its relationship with poor prognoses may be useful for the development of novel treatments for this disease.