Combination of L-3-phosphoserine phosphatase and CEA using real-time RT-PCR improves accuracy in detection of peritoneal micrometastasis of gastric cancer.
Peritoneal metastasis is the most frequent form of recurrence for advanced gastric cancer. We previously performed a global analysis of the gene expression of gastric cancer cell lines established from peritoneal metastasis with cDNA microarray. One of the up-regulated genes is L-3-phosphoserine phosphatase (L3-PP). We have examined its potential as a novel marker for the detection of peritoneal micrometastasis of gastric cancer. L3-PP mRNA in peritoneal wash from 88 gastric cancer patients was quantified for comparison of carcinoembryonic antigen (CEA) mRNA by means of real-time RT-PCR with a fluorescently-labeled probe to predict peritoneal recurrence. The quantity of L3-PP and CEA correlated with wall penetration. The cut-off value was set at the upper limit of the quantitative value of T1 cases (tumor invades within submucosa) and those above the cut-off value constituted the micrometastasis (MM+) group; eight out of 14 cases with peritoneal dissemination were MM+ L3-PP (57.1% sensitivity) and two out of 57 T1 and T2 cases were MM+ (93% specificity). For two out of 14 cases of peritoneal dissemination only L3-PP could detect micrometastasis of gastric cancer, indicating that L3-PP is superior to CEA especially in poorly-differentiated adenocarcinoma. The combination of CEA and L3-PP improved the accuracy of diagnosis up to 85.7%. Consequently, free cancer cells that cannot be detected by CEA mRNA could be detected using L3-PP mRNA. CEA alone was not sufficient, but L3-PP and CEA in combination can attain a higher accuracy of detection.
Shimomura
Katsumi
K
Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kawaramachi-dori, Kyoto 602-8566, Japan. katsumis@jb3.so-net.ne.jp
Sakakura
Chouhei
C
Takemura
Manabu
M
Takagi
Tsuyoshi
T
Fukuda
Kenichiro
K
Kin
Shuichi
S
Nakase
Yuen
Y
Miyagawa
Kouji
K
Ohgaki
Masaharu
M
Fujiyama
Junshin
J
Fujita
Yoshifumi
Y
Nakanishi
Masayoshi
M
Hagiwara
Akeo
A
Shirane
Masatomo
M
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
Yamagishi
Hisakazu
H
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology / Q000556:secondary*; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000201:enzymology / Q000276:immunology / Q000473:pathology*
D000199:Actins; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase