title: AFP mRNA detected in bone marrow by real-time quantitative RT-PCR analysis predicts survival and recurrence after curative hepatectomy for hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of General Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. t-kamiya@med.hokudai.ac.jp
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kamiyama
authors.forename: Masato
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kamachi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimamura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
authors.forename: Michiaki
authors.initials: M
authors.lastname: Matsushita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furukawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000509:alpha-Fetoproteins