Increasing tumor budding in cholangiocarcinoma is associated with decreased disease-specific survival

Abstract

Tumor budding (TB) has been shown to be an adverse prognostic factor in several gastrointestinal malignancies, most notably colorectal carcinoma (CRC). TB has undergone some evaluation in Eastern cohorts of cholangiocarcinoma (CC), and we undertook this study to evaluate whether TB in CC was linked to other clinicopathologic factors or to outcome in a Western cohort. We evaluated 112 cases of CC for age, sex, margin status, location, size, grade, lymphovascular invasion (LVI), perineural invasion (PNI), subtype (large or small duct), staging parameters, recurrence-free survival, disease-specific survival (DSS), and TB. Budding was scored using International Tumor Budding Consensus Conference recommendations for CRC: The highest tumor bud count at the invasive tumor front in a 0.785mm2 area was recorded and stratified into Bd1 (0-4 buds), Bd2 (5-9 buds), and Bd3 (≥10 buds). Our cohort included 54 (48%) extrahepatic CCs and 58 (52%) intrahepatic CCs. TB was more commonly seen in the settings of higher-grade lesions, males, extrahepatic CC, PNI, LVI, and positive resection margin (all P≤0.021). In multivariate analysis, worse DSS was correlated with budding score Bd2/Bd3 (hazard ratio [HR] 2.6687, 95% confidence interval [CI] 1.585-5.217, P=0.001) and with nodal disease (HR 2.876, 95% CI 1.585-5.217, P=0.001). TB is associated with higher-grade disease in CC, and increased TB is associated with poor disease-specific survival. Our findings support the notion that TB may serve as useful information for clinicians with respect to patient prognosis in CC, as in CRC.