Prospective evaluation of circulating hepatocytes by alpha-fetoprotein messenger RNA in patients with hepatocellular carcinoma.
BACKGROUND
The significance of alpha-fetoprotein (AFP) messenger RNA as a surrogate marker for isolated tumor cells in the blood of patients with hepatocellular carcinoma (HCC) is controversial. Our goals were to correlate AFP mRNA with tumor recurrence and overall survival after patients with HCC received curative operations and to analyze AFP mRNA findings in control patients.


METHODS
In this prospective controlled study, RNA was purified from the blood of 85 patients with HCC before, during, and after therapy and from 116 control patients. Complementary DNA synthesis by reverse transcriptase and polymerase chain reaction amplification was performed with primers specifically for the AFP gene. Patients with HCC were divided into 4 subgroups depending on the therapy performed: (1) orthotopic liver transplantation (OLT), (2) resection, (3) transarterial chemoembolization, and (4) no therapy.


RESULTS
AFP mRNA was detected in 28% of the patients with HCC and 3% of the control patients (P <.01) before therapy. Of patients with HCC and OLT, 2 of the 6 patients who were AFP mRNA positive had a recurrence; none of the 4 patients who were negative had a recurrence. In the HCC patients who underwent tumor resection or received no therapy, the survival rates did not differ between patients who were AFP mRNA positive and negative (P =.21 and P =.94, respectively). After the tumor resection, no difference in survival at 2 years was evident in patients who were AFP mRNA positive versus those who were AFP mRNA negative. In the HCC patients who had curative operations (OLT and resection) the sensitivity and specificity of this test for tumor recurrence were 73% and 53%, respectively, excluding surgical mortality. The International Union Against Cancer tumor stages in the subgroups of OLT and resection showed no differences between patients with positive and negative findings (P =.76 and P =.15, respectively). AFP mRNA results and serum AFP levels revealed no correlation (P =.45).


CONCLUSIONS
The qualitative measurement of AFP mRNA in the blood of patients with HCC is not a clinically relevant method for determining therapy and prognosis, especially if AFP mRNA is detected during the surgical procedure or any other liver manipulation.
Witzigmann
Helmut
H
Department of Surgery II and Institutes of Pathology, and Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany.
Geissler
Felix
F
Benedix
Frank
F
Thiery
Joachim
J
Uhlmann
Dirk
D
Tannapfel
Andrea
A
Wittekind
Christian
C
Hauss
Johann
J
D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000628:therapy; D016461:Chemoembolization, Therapeutic; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000628:therapy; D008297:Male; D009360:Neoplastic Cells, Circulating; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D000509:alpha-Fetoproteins