Prognostic Significance of Tumor Budding in Patients with Resected Perihilar Cholangiocarcinoma

Introduction: Tumor budding (TB), a type of diffusely infiltrative growth observed in many gastrointestinal cancers, is a well-established adverse prognostic factor. To the best of our knowledge, prognostic significance of TB in perihilar cholangiocarcinoma (PHC) have not been reported. We aimed to assess the prognostic significance of TB in PHC, and determine its relationship with other clinicopathologic features. Methods: Between January 2004 and December 2017, 81 patients with PHC underwent surgical resection and in these patients various prognostic factors were examined. TB was defined as tumor cells or clusters composed of less than 5 cells at the invasive tumor front per field using 20 times objective lens in specimen stained with H&E. TB was classified into two groups: low-TB(<5/field) and high-TB(≥5/field), and compared with clinicopathological features. Results: A multivariate analysis revealed that LN metastasis (HR3.894, p = 0.048) residual tumor (9.533, p = 0.002), and high-TB (HR11.147, p = 0.001) were identified as independent poor prognostic factors. Eighty-one patients were divided into low-TB(n = 57, 2.0 ± 1.5/field) and high-TB groups(n = 24, 9.5 ± 3.5/field). By comparing low-TB vs. high-TB groups, the following rates were significantly higher in high-TB groups: combined PV resection (38.6% vs. 66.7%, p = 0.028), tumor-stage III or more (42.1% vs. 70.8%, p = 0.028), LN metastasis (40.4% vs. 70.8%, p = 0.016), intrahepatic metastasis (1.8% vs. 20.8%, p = 0.008), and poor differentiation (5.3% vs. 25.0%, p = 0.019). Disease specific 5-year survival rate was 44.2% (MST:52.4M) in Low-TB group and 9.5% (MST:19.4M) in high-TB group, as shown in Figure. Conclusion: High-TB at the invasive front of tumors could be a novel prognostic factor in resected PHC.