Clinical significance of alpha-fetoprotein mRNA in blood of patients with hepatocellular carcinoma.
BACKGROUND
Alpha-fetoprotein (AFP) messenger RNA (mRNA) in the blood reflects the presence of circulating hepatocellular carcinoma (HCC) cells and is a sensitive marker of HCC extrahepatic metastases. The specificity of this molecular marker and its correlation with the main HCC clinical-pathological parameters remains controversial, however.


METHODS
AFPmRNA was determined in 50 HCC patients and in 50 patients with diagnosis of cirrhosis (6), or colon (24) or, pancreatic (20) carcinoma. HCC patients with clinically evident extrahepatic metastasis were excluded. HCC diagnosis was confirmed in all patients by histology on percutaneous biopsies or surgical specimens; pathological grading was assessed at the same time.


RESULTS
AFPmRNA was positive in 20 HCC patients (40%) and in 18 patients without HCC (36%). The presence of AFPmRNA in the blood correlated significantly with cholestatic indices (p<0.01), nodule size (p=0.03), vascular invasion (p=0.006) and moderately or poorly differentiated HCC (p<0.0001). Moreover, survival analysis showed a significant impact of AFPmRNA detection on overall (p=0.04) and recurrence-free survival (p=0.0007) after a median follow-up of 17 months.


CONCLUSIONS
Although AFPmRNA is frequently detected in the blood, even in benign liver diseases or gastroenteric tumors, in HCC patients without clinical evidence of extrahepatic metastases it seemed to identify the biologically more aggressive tumors.
Cillo
Umberto
U
Clinica Chirurgica I, Department of Surgical and Gastroenterological Sciences, University of Padua, School of Medicine, Via Giustiniani 2, Policlinico III Piano, 35128 Padova, Italy.
Navaglia
Filippo
F
Vitale
Alessandro
A
Molari
Alfiero
A
Basso
Daniela
D
Bassanello
Marco
M
Brolese
Alberto
A
Zanus
Giacomo
G
Montin
Umberto
U
D'Amico
Francesco
F
Ciarleglio
Francesco Antonio
FA
Carraro
Amedeo
A
Bridda
Alessio
A
Burra
Patrizia
P
Carraro
Paolo
P
Plebani
Mario
M
D'Amico
Davide Francesco
DF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000097:blood; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000302:isolation & purification; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood; D010190:Pancreatic Neoplasms / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D000509:alpha-Fetoproteins