Association between recurrence of hepatocellular carcinoma and alpha-fetoprotein messenger RNA levels in peripheral blood.
OBJECTIVE
Intra- and extrahepatic recurrence is common, even after curative resection for hepatocellular carcinoma (HCC), suggesting preoperative or intraoperative tumor cell dissemination. Reverse transcription - polymerase chain reaction (RT-PCR) for alpha-fetoprotein (AFP) is used to detect circulating liver cancer cells. We previously developed a quantitative method that allows estimation of the AFP mRNA level by real-time PCR. In the present study, we used this method to measure the AFP mRNA level before and after resection of HCC, then correlated the findings with various clinicopathological characteristics and prognosis.


METHODS
We prospectively examined peripheral blood samples from 38 patients with HCC, and bone marrow aspirate from 25 of these patients. As a control, we examined bone marrow from 20 patients with benign diseases. The follow-up period ranged from 32 to 66 months. Real-time RT-PCR was used to detect AFP mRNA levels in the samples.


RESULTS
AFP was expressed in 9 (23.7%) of the 38 peripheral blood samples. The detection of AFP mRNA was significantly correlated with extrahepatic metastasis after primary surgery, and a shorter disease-free survival time (P = 0.0245 each). Bone marrow samples were defined as positive if they expressed AFP mRNA at levels higher than the maximum expressed level in the controls, because only 1 (5%) of the 20 control bone marrow samples had low AFP mRNA expression. Using this cutoff level, 12 (48%) of the 25 patients with HCC had positivity for AFP mRNA. The results of bone marrow RT-PCR did not correlate with the clinocopathological characteristics of prognosis.


CONCLUSIONS
Using real-time PCR to measure the AFP mRNA level in blood, but not bone marrow, could be useful for predicting postoperative tumor recurrence.
Morimoto
Osakuni
O
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Japan.
Nagano
Hiroaki
H
Miyamoto
Atsushi
A
Fujiwara
Yoshiyuki
Y
Kondo
Motoi
M
Yamamoto
Tameyoshi
T
Ota
Hideo
H
Nakamura
Masato
M
Wada
Hiroshi
H
Damdinsuren
Bazarragchaa
B
Marubashi
Shigeru
S
Dono
Keizo
K
Umeshita
Koji
K
Nakamori
Shoji
S
Sakon
Masato
M
Monden
Morito
M
D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood*; D018709:Statistics, Nonparametric; D000509:alpha-Fetoproteins / Q000378:metabolism*
D012333:RNA, Messenger; D000509:alpha-Fetoproteins