The Role of Pan-Cytokeratin In Tumor Budding Upgrading In Malignant Colorectal Polyps At Stage pT1.

Purpose: Tumor budding (TB) is an established prognostic factor in early colorectal cancer. However, its evaluation on hematoxylin-eosin (H&E) slides may underestimate the true budding activity. This study aimed to investigate the role of pan-cytokeratin (Pan-CK) immunohistochemistry in upgrading TB assessment in malignant colorectal polyps at the pT1 stage and to determine clinicopathological factors associated with TB upgrading. Patients and Methods: We retrospectively reviewed 104 malignant colorectal polyps at the pT1 stage diagnosed between January 2015 and June 2024 at the University Medical Center, Ho Chi Minh City. TB was assessed on H&E and Pan-CK stained slides according to the 2016 International Tumor Budding Consensus Conference (ITBCC) criteria. Cases were classified as Bd1 (0-4 buds), Bd2 (5-9 buds), or Bd3 (≥10 buds). Upgrading was defined as an increase in TB grade on Pan-CK compared with H&E, particularly evaluated among cases classified as Bd1 on H&E. Clinicopathological features associated with upgrading were analyzed using univariate and multivariate models. Results: The number of tumor buds was significantly higher on Pan-CK compared with H&E (median [IQR] 1.0 [0.0-7.0] vs 0.5 [0.0-3.0]; p < 0.001). Among 90 cases classified as Bd1 on H&E, 25 (27.78%) were upgraded to Bd2/3 after Pan-CK staining. In univariate analysis, higher Haggitt/Kikuchi level and the presence of synchronous polyps were significantly associated with upgrading, whereas tumor grade 2 demonstrated a borderline association. Multivariate analysis identified synchronous polyps as the only independent predictor (OR = 3.00, 95% CI: 1.03-8.76; p = 0.045). Conclusion: Pan-CK substantially increases TB detection and grading in pT1 malignant colorectal polyps. Synchronous polyps were identified as the sole independent predictor of TB upgrading, representing a novel finding. Selective Pan-CK use in these cases may optimize resources and guide management.