Clinical features and prognosis of hepatocellular carcinoma with reference to serum alpha-fetoprotein levels. Analysis of 606 patients

Abstract

Clinical features of hepatocellular carcinoma (HCC) with normal serum alpha-fetoprotein (AFP) levels were compared with those of AFP-positive cases. A total of 606 patients were divided into four groups based on their serum AFP levels at the time of diagnosis: group 1 (less than or equal to 20 ng/ml, N = 125), group 2 (20-1000 g/ml, N = 256), group 3 (1000-10000 ng/ml, N = 149), and group 4 (greater than 10000 ng/ml, N = 76). Increasing prevalence of group 1 patients and decreasing prevalence of group 4 were noted during the last 9 years. The proportion of hepatitis B virus-positive cases was significantly lower in group 1 than in group 4. The serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase ratio was found to be significantly higher in group 4 than in group 1 regardless of the size of the tumors. The survival rates were compared among the four groups in size matched cases since the size of the tumor significantly influenced their prognosis. The median survival in relatively small HCC patients (less than or equal to 5 cm in diameter, N = 199) were 24.6 months for group 1, 20.6 months for group 2, and 13.7 months for group 3 patients; and those in large HCC (greater than 50% in the proportion of the tumor area, N = 200) were 15.1 months for group 1, 6.3 months for group 2, 5.8 months for group 3, and 5.2 months for group 4. Thus, serum AFP values at the time of presentation are not only of diagnostic value, but also of prognostic significance in patients with HCC.

Serum α-Fetoprotein Response as a Surrogate for Clinical Outcome in Patients Receiving Systemic Therapy for Advanced Hepatocellular Carcinoma

“…Normally produced by the fetal yolk sac, liver, and intestine, elevated levels can be associated with HCC in the appropriate clinical setting [11]. Previous studies have documented that the level of AFP at diagnosis may be predictive of patient survival [12][13][14][15]. The specificity for the diagnosis of HCC has been estimated at roughly 91%, based on a reference value of Ͻ20 ng/ml.…”

High α‐fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: Significance of hepatitis virus infection, age, p53 and β‐catenin mutations

“…Chromosome 4q is one of the most frequent chromosomal region exhibiting allelic losses in hepatocellular carcinoma (HCC), 4 -7 whereas AFP expression resurges during liver regeneration 8 and in HCC. 2,8 -10 The AFP elevation in HCC has been shown to correlate with poor tumor differentiation, 9,10 tumor burden, 11 early recurrence after tumor resection 12,13 and unfavorable prognosis. 11 Serum AFP elevation concurrent with aberrant growth is usually regarded as coincidental, and its role in HCC progression receives little attention.…”

“…2,8 -10 The AFP elevation in HCC has been shown to correlate with poor tumor differentiation, 9,10 tumor burden, 11 early recurrence after tumor resection 12,13 and unfavorable prognosis. 11 Serum AFP elevation concurrent with aberrant growth is usually regarded as coincidental, and its role in HCC progression receives little attention. However, cumulative evidence has shown that AFP plays an important role in the regulation of tumor growth and cell differentiation 14 -17 and can stimulate proliferation of human hepatoma cells, probably through the AFP receptors.…”

“…23,24 Clinically, AFP elevation in sera or AFP mRNA expression in HCC occurs more often in HCC patients of younger age 9 and positive for serum HBsAg. 10,11 But the molecular mechanism is not fully understood. The tumor suppressor p53 acts through its binding within the AFP repressor region, displacing bound HNF-3 and altering the chromatin structure at the core promoter, to repress AFP gene expression.…”

Staging of Hepatocellular Carcinoma

“…2 Out of the various biomarkers, alpha feto protein (AFP) has been studied in detail and has a role both in diagnosis and prognosis of HCC. 3 Other biomarkers include cellular malignancy phenotype related markers like DNA ploidy, cellular proliferation markers (PCNA, Ki 67 etc), p53 gene, tumor promoter genes (ras, c-myc), apoptosis related markers like Fas and Fas ligand, cell adhesion and extracellular matrix related markers like adhesive molecules (E-adherin, catenins, SI-CAM etc), angiogenesis related markers like vascular endothelial growth factor (VEGF), platelet derived-ECGF, intra tumor vascular density (ITVD) and genomics and proteomics related markers. 2 All above-mentioned prognostic markers can be used either singly or as combination of various markers.…”