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.
Clinica Chirurgica I, Department of Surgical and Gastroenterological Sciences, University of Padua, School of Medicine, Via Giustiniani 2, Policlinico III Piano, 35128 Padova, Italy.
Umberto
U
Cillo
Filippo
F
Navaglia
Alessandro
A
Vitale
Alfiero
A
Molari
Daniela
D
Basso
Marco
M
Bassanello
Alberto
A
Brolese
Giacomo
G
Zanus
Umberto
U
Montin
Francesco
F
D'Amico
Francesco Antonio
FA
Ciarleglio
Amedeo
A
Carraro
Alessio
A
Bridda
Patrizia
P
Burra
Paolo
P
Carraro
Mario
M
Plebani
Davide Francesco
DF
D'Amico
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