AFP mRNA detected in bone marrow by real-time quantitative RT-PCR analysis predicts survival and recurrence after curative hepatectomy for hepatocellular carcinoma.
OBJECTIVE
To determine whether detection of hepatocellular carcinoma (HCC) cells by real-time quantitative RT-PCR targeting of alpha-fetoprotein mRNA (AFP mRNA) before or after curative hepatectomy predicts HCC recurrence and patient survival.


BACKGROUND
The presence of cancer cells in peripheral blood and/or bone marrow in patients with malignant disease has been reported to correlate with outcome.


METHODS
Between July 2000 and June 2005, 136 consecutive HCC patients underwent primary curative hepatectomy. Bone marrow aspirated preoperatively, and peripheral blood samples collected before and after operation were subjected to real-time quantitative RT-PCR analysis using AFP mRNA as a target molecule. Median follow-up was 23 months (range, 6-54 months). Patient survival (PS), disease-free survival (DFS), and clinicopathologic features were compared between patients with positive and negative AFP mRNA.


RESULTS
Twenty-four patients died (22 from HCC). HCC recurred in 66 patients (hepatic in 37 [56.1%]; hepatic and remote in 17 [25.8%], and remote alone in 12 [18.2%]). Bone marrow was positive for AFP mRNA in 38 patients (27.9%) and negative in 98 (72.1%). One- and 3-year PS was 96.6% and 91.4%, respectively, with negative AFP mRNA versus 86.2% and 55.5%, respectively, with positive AFP mRNA (P < 0.0001). One- and 3-year DFS were 73.2% and 44.8%, respectively, with negative AFP mRNA versus 54.5% and 25.8%, respectively, with positive AFP mRNA (P = 0.0399). Portal vascular invasion, tumor size, multiple tumors, and tumor differentiation correlated with inferior PS and DFS on univariate analysis. On multivariate analysis, positive AFP mRNA was the most important risk factor for PS (P = 0.001) and DFS (P = 0.0165). In addition, positive AFP mRNA in peripheral blood after operation tended to predict reduced DFS.


CONCLUSIONS
AFP mRNA in the bone marrow and systemic circulation during the perioperative period predicts patient survival and recurrence after curative hepatic resection for HCC.
Kamiyama
Toshiya
T
Department of General Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. t-kamiya@med.hokudai.ac.jp
Takahashi
Masato
M
Nakagawa
Takahito
T
Nakanishi
Kazuaki
K
Kamachi
Hirofumi
H
Suzuki
Tomomi
T
Shimamura
Tsuyoshi
T
Taniguchi
Masahiko
M
Ozaki
Michitaka
M
Matsushita
Michiaki
M
Furukawa
Hiroyuki
H
Todo
Satoru
S
D014408:Biomarkers, Tumor / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D012333:RNA, Messenger / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000509:alpha-Fetoproteins