Cancer Res Treat.  2016 Jan;48(1):180-189. 10.4143/crt.2014.321.

The Prognostic Role of Mitotic Index in Hepatocellular Carcinoma Patients after Curative Hepatectomy

• Ha SY
• Choi M
• Lee T
• Park CK

• KMID: 2152274
• DOI: http://doi.org/10.4143/crt.2014.321

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 determined. 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 hematoxylin 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 Committee 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.

Keyword

Mitotic index; Prognostic factor; Survival; Hepatocellular carcinoma

MeSH Terms

alpha-Fetoproteins
Carcinoma, Hepatocellular*
Cell Proliferation
Hematoxylin
Hepatectomy*
Hepatitis B virus
Humans
Joints
Liver Cirrhosis
Liver Neoplasms
Mitotic Index*
Neoplasm Metastasis
Portal Vein
Prognosis
Hematoxylin
alpha-Fetoproteins

Figure

• 

  Fig. 1. Microscopic features of hepatocellular carcinomas. (A) A case of low mitotic index showing no mitotic cells. (B) A case of high mitotic index showing many mitotic cells (arrows) (A and B, H&E staining, ×400).

• 

  Fig. 2. Kaplan-Meier survival curves by log-rank test showing recurrence-free survival (A) and disease-specific survival (B) according to the mitotic index in 282 hepatocellular carcinomas.

• 

  Fig. 3. Kaplan-Meier survival curves by log-rank test showing disease-specific survival according to the mitotic index in subgroups by tumor size (A, B), microvascular invasion (C, D), intrahepatic metastasis (E, F), American Joint Committee on Cancer (AJCC) T-stage (G, H), and Barcelona Clinic Liver Cancer (BCLC) stage (I, J).

Reference

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