The Prognostic Role of Mitotic Index in Hepatocellular Carcinoma Patients after Curative Hepatectomy
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Purpose High proliferation rate is a hallmark of cancer. The mitotic index is a useful and simple method for analysis of cell proliferation. However, the practical utility of mitotic index as a predictor of prognosis in patients with hepatocellular carcinoma (HCC) has not been deter- mined. Therefore, we examined mitotic index as a prognostic marker in HCC patients. Materials and Methods We counted the number of mitotic cells in 10 high-power fields of the tumor area on hema- toxylin and eosin–stained slides representing 282 surgically resected HCCs. The highest number of mitotic cells was defined as the mitotic index. Results High mitotic index was observed in 127 of 282 HCCs. High mitotic index showed significant association with younger age, larger tumor size, higher Edmondson grade, microvascular invasion, major portal vein invasion, intrahepatic metastasis, higher American Joint Com- mittee on Cancer (AJCC) T-stage, higher Barcelona Clinic Liver Cancer (BCLC) stage, higher alpha-fetoprotein level, hepatitis B virus etiology, and liver cirrhosis. Patients with high mitotic index had shorter disease-specific survival (DSS) (p < 0.001) and tended to have shorter recurrence-free survival (p=0.112). In subgroup analysis among patients with a larger tumor size, microvascular invasion, intrahepatic metastasis, higher AJCC T-stage, and higher BLCL stage, high mitotic index showed unfavorable influences on DSS (p=0.001, p=0.008, p=0.003, p=0.012, and p < 0.001, respectively). In addition, high mitotic index was an independent predictor of shorter DSS (p=0.004). Conclusion High mitotic index may be a novel predictor of DSS in patients with HCC and may have utility as an auxiliary prognostic factor in HCC.
Abstract
Purpose High proliferation rate is a hallmark of cancer. The mitotic index is a useful and simple method for analysis of cell proliferation. However, the practical utility of mitotic index as a predictor of prognosis in patients with hepatocellular carcinoma (HCC) has not been deter- mined. Therefore, we examined mitotic index as a prognostic marker in HCC patients. Materials and Methods We counted the number of mitotic cells in 10 high-power fields of the tumor area on hema- toxylin and eosin–stained slides representing 282 surgically resected HCCs. The highest number of mitotic cells was defined as the mitotic index. Results High mitotic index was observed in 127 of 282 HCCs. High mitotic index showed significant association with younger age, larger tumor size, higher Edmondson grade, microvascular invasion, major portal vein invasion, intrahepatic metastasis, higher American Joint Com- mittee on Cancer (AJCC) T-stage, higher Barcelona Clinic Liver Cancer (BCLC) stage, higher alpha-fetoprotein level, hepatitis B virus etiology, and liver cirrhosis. Patients with high mitotic index had shorter disease-specific survival (DSS) (p < 0.001) and tended to have shorter recurrence-free survival (p=0.112). In subgroup analysis among patients with a larger tumor size, microvascular invasion, intrahepatic metastasis, higher AJCC T-stage, and higher BLCL stage, high mitotic index showed unfavorable influences on DSS (p=0.001, p=0.008, p=0.003, p=0.012, and p < 0.001, respectively). In addition, high mitotic index was an independent predictor of shorter DSS (p=0.004). Conclusion High mitotic index may be a novel predictor of DSS in patients with HCC and may have utility as an auxiliary prognostic factor in HCC.
참고문헌 (20)
- Okuda K, "Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850patients", Cancer, 56, pp.918~928 (1985)
- Llovet JM, "Resection and liver transplantation for hepatocellular carcinoma", Semin Liver Dis, 25, pp.181~200 (2005)
- Poon RT, "Prevention of recurrence after resection of hepatocellular carcinoma : a daunting challenge", Hepatology, 54, pp.757~759 (2011)
- Hanahan D, "The hallmarks of cancer", Cell, 100, pp.57~70 (2000)
- Ouchi K, "Mitotic index is the best predictive factor for survival of patients with resected hepatocellular carcinoma", Dig Surg, 17, pp.42~48 (2000)
- Tannapfel A, "Apoptosis and proliferation in relation to histopathological variables and prognosis in hepatocellular carcinoma", J Pathol, 187, pp.439~445 (1999)
- Romani AA, "The expression of HSP27 is associated with poor clinical outcome in intrahepatic cholangiocarcinoma", BMC Cancer, 7, pp.232~ (2007)
- Bloom HJ, "Histological grading and prognosis in breast cancer : a study of 1409 cases of which 359 have been followed for 15 years", Br J Cancer, 11, pp.359~377 (1957)
- Vang R, "Ovarian low-grade and highgrade serous carcinoma : pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems", Adv Anat Pathol, 16, pp.267~282 (2009)
- Edge SB, "AJCC cancer staging manual" (2010), Springer
- Haratake J, "Predictable factors for estimating prognosis of patients after resection of hepatocellular carcinoma", Cancer, 72, pp.1178~1183 (1993)
- Nanashima A, "Fibrosis and inflammatory activity in noncancerous tissue and mitotic index of cancer tissue in patients with hepatocellular carcinoma : relationship to clinicopathological factors and prognosis after hepatic resection", Dig Dis Sci, 48, pp.1517~1522 (2003)
- Edmondson HA, "Primary carcinoma of the liver : a study of 100 cases among 48, 900 necropsies", Cancer, 7, pp.462~503 (1954)
- Liver Cancer Study Group of Japan, "General rules for the clinical and pathological study of primary liver cancer" (2003), Kanehara
- Shimada M, "Characteristics of multicentric hepatocellular carcinomas : comparison with intrahepatic metastasis", World J Surg, 25, pp.991~995 (2001)
- Imamura H, "Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy", J Hepatol, 38, pp.200~207 (2003)
- Llovet JM, "Prognosis of hepatocellular carcinoma : the BCLC staging classification", Semin Liver Dis, 19, pp.329~338 (1999)
- Hoshida Y, "Gene expression in fixed tissues and outcome in hepatocellular carcinoma", N Engl J Med, 359, pp.1995~2004 (2008)
- Baak JP, "Mitosis counting in tumors", Hum Pathol, 21, pp.683~685 (1990)
- Camp RL, "X-tile : a new bioinformatics tool for biomarker assessment and outcome-based cut-point optimization", Clin Cancer Res, 10, pp.7252~7259 (2004)