Combination of L-3-phosphoserine Phosphatase and CEA Using Real-time RT-PCR Improves Accuracy in Detection of Peritoneal Micrometastasis of Gastric Cancer
2004
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. Peritoneal dissemination represents 60-70% of the forms of advanced gastric cancer recurrence, however there are few reports of the gene groups involved in the peritoneal dissemination mechanism (1). We previously reported the effects of intraperitoneally administered mitomycin C adsorbed on activated carbon (MMC-CH) for the prevention of relapse of gastric cancer with serosal invasion (2). However, the intraperitoneal dosage of anticancer drugs such as MMC-CH can have some side-effects including ileus and leukocytopenia, and it is necessary to identify intraperitoneal free cancer cells during an operation. Peritoneal lavage cytology is generally performed to detect floating cancer cells at the beginning of an operation to evaluate the possibility of peritoneal dissemination (3, 4). Intraperitoneal free cancer cells are recognized as one of the most important prognosis-determining factors. However, the
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