PROSPECTIVE EVALUATION OF CIRCULATING HEPATOCYTES BY ALPHA-FETOPROTEIN MESSENGER-RNA IN HUMANS DURING LIVER SURGERY

Objective The objective of this study was to analyze the specificity o f detecting liver tumor cell dissemination by alpha-fetoprotein (AFP) mRNA in peripheral blood. Summary Background Data Alpha-fetoprotein mR NA has been used for the detection of circulating micrometastatic tumo r foci of hepatocellular carcinoma (HCC); however, the interpretation of the results has been equivocal. Methods Sixty-four consecutive pati ents with malignant HCC (n = 20), liver metastases (n = 27), or nonmal ignant (n = 17) liver diseases undergoing partial or total hepatectomy and orthotopic liver transplantation were included in this prospectiv e study from January to July 1995. Peripheral blood samples were obtai ned before surgery, during surgery, and after surgery (range, 6-15 mon ths). Total mRNA was extracted from nucleated cells, and cDNA synthesi s and polymerase chain reaction amplification (nested polymerase chain reaction in one tube) were performed with specific AFP primers. Resul ts Preoperative AFP mRNA was detected in 20 patients (17%), of which 5 of 20 had HCC. Intraoperative assessment showed positive AFP mRNA val ues in a total of 34 patients (53%) with various causes, of which 8 of 20 (40%) had HCC, 17 of 27 (63%) had other malignancies, and 9 of 17 (53%) had nonmalignant diseases. Recurrent tumor in patients with HCC occurred in four cases after surgery (range, 6-15 months) and did not correlate with AFP mRNA positivity before surgery, during surgery, or after surgery, Conclusions Alpha-fetoprotein mRNA in peripheral blood is not a specific marker of circulating micrometastases from HCC, espe cially in the context of surgical treatment of HCC.