Triple positive tumor markers predict recurrence and survival in early stage hepatocellular carcinoma.
OBJECTIVE
Hepatectomy is feasible for patients with hepatocellular carcinoma (HCC) with good hepatic function who meet the Milan criteria. Several studies have indicated that tumor markers of HCC, α-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP percentage and protein induced by vitamin K absence/antagonist-II were good predictors of malignant potential. It is important to identify highly malignant cases of HCC, and the aim of this study was to clarify the impact of triple positive tumor markers as the prognostic factors for early stage HCC within the Milan criteria.


METHODS
This study investigated 199 patients who underwent hepatectomy for HCC within the Milan criteria between January 2001 and May 2009. Cumulative recurrence-free survival (RFS), overall survival (OS) and clinicopathological parameters were analyzed according to the number of positive tumor markers.


RESULTS
In patients with triple positive tumor markers, 5-year RFS and OS was poor (17.1 and 61.4%, respectively). Multivariate analyses revealed independent risk factors for recurrence to be hepatitis C virus antibody positivity, non-initial treatment for HCC and triple positive tumor markers, and the independent risk factors for OS were high indocyanine green retention rate at 15 min value, maximum tumor size and triple positive tumor markers. Pathologically invasive growth, microvascular invasion and moderate to poor differentiation were significantly related to the number of the three tumor markers.


CONCLUSIONS
Triple positive tumor markers for early stage HCC within the Milan criteria showed poor prognosis and malignant characteristics. These markers could be a useful predictor for the degree of malignant potential in early stage HCC.
Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.
Shigeki
S
Nakagawa
Toru
T
Beppu
Hirohisa
H
Okabe
Keita
K
Sakamoto
Hideyuki
H
Kuroki
Kosuke
K
Mima
Hidetoshi
H
Nitta
Katsunori
K
Imai
Hiromitsu
H
Hayashi
Yasuo
Y
Sakamoto
Daisuke
D
Hashimoto
Akira
A
Chikamoto
Takatoshi
T
Ishiko
Masayuki
M
Watanabe
Hideo
H
Baba
alpha-fetoprotein; des-γ-carboxy prothrombin; hepatocellular carcinoma; prognosis; protein induced by vitamin K absence/antagonist-II