Prognostic Role of Mitotic Index in Hepatocellular Carcinoma: Potential Clinical Implications for Very Early Stage Disease

Sangjoon Choi,1,2,* Yoon Ah Cho,2,3,* Sujin Park,1 Hyun Hee Koh,4 Boram Park,5,6 Kyunga Kim,5 Ju Dong Yang,7 Sang Yun Ha2 1Pathology Center, Shinwon Medical Foundation, Gwangmyeong-si, Republic of Korea; 2Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 3Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 4Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea; 6College of Medicine, Inha University, Incheon, Republic of Korea; 7Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA*These authors contributed equally to this workCorrespondence: Sang Yun Ha, Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea, Tel +82 234101586, Fax +82 234100025, Email [email protected]: Surgical resection and ablation therapy are both primary treatment options for very early stage hepatocellular carcinoma (HCC). Accurate risk stratification is important, since patients at higher risk of recurrence may derive greater benefit from curative resection than from ablation. We investigated whether the mitotic index is associated with early recurrence in HCC and may serve as a prognostic marker to refine risk assessment in very early stage disease.Methods: The number of mitoses was counted in representative tumor slides from 942 cases of surgically resected HCC from Samsung Medical Center. A high mitotic index was defined as more than eight mitoses in 10 high-power fields. The relationship between mitotic index, clinicopathological characteristics, and prognosis were analyzed. External validation was performed using 112 HCC cases obtained from Hallym University Sacred Heart Hospital.Results: High mitotic index was identified in 296 patients and was significantly associated with aggressive clinicopathological features including higher Edmondson grade, advanced American Joint Committee on Cancer T stage, and early tumor recurrence. Patients with a high mitotic index displayed a significantly shorter early recurrence-free survival (e-RFS). In subgroup analysis of patients with very early stage, the high mitotic index group showed unfavorable influences on e-RFS.Conclusion: High mitotic index is a significant predictor of early recurrence in HCC patients and may provide useful prognostic information in very early stage disease. While its direct role in guiding primary treatment selection is limited, the mitotic index could contribute to risk stratification and postoperative management strategies.Keywords: hepatocellular carcinoma, prognosis, recurrence, mitosis, mitotic index

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