Development of a multiple-marker RT-PCR assay for detection of micrometastases of hepatocellular carcinoma.
We investigated the expression of several candidate gene markers: MAGE-1, MAGE-3, cytokeratin-20 (CK-20), and alpha-fetoprotein (AFP) in tumor tissue and blood specimens from patients with hepatocellular carcinoma to develop a multiple marker reverse transcriptase-polymerase chain reaction (RT-PCR) assay for detection of micrometastasis in circulation. In 24 tumor specimens, the positivity for MAGE-1, MAGE-3, AFP, and CK-20 genes was 71, 67, 88, and 79% respectively, and all specimens expressed at least one marker. Although AFP and CK-20 transcripts were also detected in corresponding noncancerous liver specimens, none of the 22 corresponding normal specimens or seven normal livers were positive for MAGE-1 or MAGE-3 transcripts. In addition, MAGE-1 and MAGE-3 gene transcripts were not detected in any peripheral blood specimens from 31 normal healthy volunteers. MAGE-1, MAGE-3, and AFP transcripts were detected in 9 (12.7%), 3 (4.8%), and 10 (15.9%) of 71 blood specimens from 11 hepatocellular carcinoma patients, respectively, while 19 specimens (26.8%) were positive for at least one marker. Our results indicate that a multimarker RT-PCR assay with cancer-specific markers such as MAGE-1 and MAGE-3 in combination with a liver-specific AFP marker may be a promising diagnostic tool for monitoring hepatocellular carcinoma patients with better sensitivity and specificity.
Miyamoto
A
A
Second Department of Surgery, Osaka University Medical School, Suita-City, Japan.
Fujiwara
Y
Y
Sakon
M
M
Nagano
H
H
Sugita
Y
Y
Kondo
M
M
Eguchi
H
H
Dono
K
K
Umeshita
K
K
Nakamori
S
S
Monden
M
M
D001790:Blood Physiological Phenomena; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary*; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D005819:Genetic Markers