Pretreatment platelet count early predicts extrahepatic metastasis of human hepatoma.
OBJECTIVE
Thrombocytosis is associated with metastasis in many human cancers. Most hepatocellular carcinomas (HCC) develop in cirrhotic livers, which are characterized by thrombocytopenia. We aimed to elucidate the pretreatment platelet count in prediction of extrahepatic metastasis of HCC during the follow-up.


METHODS
Three cohorts containing 1660, 480 and 965 HCC patients enrolled from three hospitals were used for discovery and validation respectively. Pretreatment clinical factors associated with extrahepatic metastasis during follow-up up to 5 years were identified using multivariate Cox regression model.


RESULTS
In early-stage HCC (BCLC stage 0-A), pretreatment platelet count (hazard ratio [HR], 1.04 per 10,000/μl; 95% CI, 1.01-1.07; P = 0.010) and serum alpha-foetoprotein (AFP) >100 ng/ml (HR, 1.70; 95% CI, 1.04-2.78; P = 0.033) were the only two independent factors associated with extrahepatic metastasis. Receiver operating characteristic evidenced that pretreatment platelet count predicted metastasis better than AFP did. Survival tree analysis identified platelet counts <118,000/μl (HR, 0.49; 95% CI, 0.38-0.63; P < 0.001) or >212,000/μl (HR, 2.12; 95% CI, 1.67-2.70; P < 0.001) to categorize patients into low and high risk of metastasis subgroups, which were verified using both validation cohorts.


CONCLUSIONS
Pretreatment platelet count is a reliable marker to predict extrahepatic metastasis of early-stage HCC following curative treatment. Cirrhotic thrombocytopenia contributes to relatively low metastasis incidence of HCC than many other cancers. High platelet count identifies a subgroup of HCC patients at high risk of metastasis, who might benefit from adjuvant therapies following initial curative treatment.
Department of General Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Chern-Horng
CH
Lee
Resource Center for Clinical Research, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Yu-Jr
YJ
Lin
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Chen-Chun
CC
Lin
Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
Cho-Li
CL
Yen
Department of Gastroenterology and Hepatology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
Chien-Heng
CH
Shen
Resource Center for Clinical Research, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Chee-Jen
CJ
Chang
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.|Liver Research Unit, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.|Clinical Proteomics Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.|Chang Gung University College of Medicine, Taoyuan, Taiwan.
Sen-Yung
SY
Hsieh
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D010976:Platelet Count; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013922:Thrombocytosis / Q000150:complications*; D000509:alpha-Fetoproteins / Q000032:analysis
D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins
cirrhosis; hepatocellular carcinoma; metastasis; platelet