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

Huy Minh Le,1 Phat Thi Hong Ho,1 Hanh Thi Tuyet Ngo,1 Minh Hoang Dang,1 Thang Quoc Pham,1 Giang Huong Tran,1,2 Duy Duc Nguyen2 1Department of Histology, Embryology, and Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Pathology Department, University Medical Center Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Phat Thi Hong Ho, Department of Histology, Embryology, and Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang Street, Cho Lon Ward, Ho Chi Minh City, 700000, Vietnam, Tel +84362684139, Email [email protected] Duy Duc Nguyen, Department of Pathology, University Medical Center Ho Chi Minh City, 215 Hong Bang Street, Cho Lon Ward, Ho Chi Minh City, 700000, Vietnam, Tel +84904974422, Email [email protected]: 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.Keywords: immunohistochemistry, early colorectal carcinoma, submucosal invasion, tumor budding