AIM: To explore the relationship between α-fetoprotein (AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma (HCC) thoroughly.

METHODS: A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study. The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis, such as status of hepatitis B virus (HBV) infection, tumor size, tumor number, vascular invasion and degree of tumor differentiation. Also, patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP (≤ 20 μg/L, 21-400 μg/L, 401-800 μg/L, and≥ 801 μg/L), to compare the positive rate of patient among four groups stratified by various clinicopathological variables. And the correlation of different kinds of tumor staging systems, such as TNM, Barcelona Clinic Liver Cancer (BCLC) staging classification and China staging, were compared with the serum concentration of AFP.

RESULTS: A total of 2304 HCC patients were enrolled in this study totally; the mean serum level of AFP was 555.3±546.6 μg/L. AFP levels were within the normal range (< 20 μg/L) in 27.4%(n= 631) of all the cases. 81.4%(n= 1875) patients were infected with HBV, and those patients had much higher serum AFP level compared with non-HBV infection ones (573.9±547.7 μg/L vs 398.4±522.3 μg/L, P< 0.001). The AFP level in tumors≥ 10 cm (808.4±529.2 μg/L) was significantly higher (P< 0.001) than those with tumor size 5-10 cm (499.5±536.4 μg/L) and with tumor size≤ 5 cm (444.9±514.2 μg/L). AFP levels increased significantly in patients with vascular invasion (694.1±546.9 μg/L vs 502.1±543.1 μg/L, P< 0.001). Patients with low tumor cell differentiation (559.2±545.7 μg/L) had the significantly (P= 0.007) highest AFP level compared with high differentiation (207.3±420.8 μg/L) and intermediate differentiation (527.9±538.4 μg/L). In the multiple variables analysis, low tumor cell differentiation [OR 6.362, 95% CI: 2.891-15.382, P= 0.006] and tumor size (≥ 10 cm)(OR 5.215, 95% CI: 1.426-13.151, P= 0.012) were independent predictors of elevated AFP concentrations (AFP> 400 μg/L). Serum AFP levels differed significantly (P< 0.001) in the D stage of BCLC (625.7±529.8 μg/L) compared with stage A (506.2±537.4 μg/L) and B (590.1±551.1 μg/L).

CONCLUSION: HCC differentiation, size and vascular invasion have strong relationships with AFP, poor differentiation and HCC size≥ 10 cm are independent predictors of elevated AFP. BCLC shows better relationship with AFP