Combination of L-3-phosphoserine phosphatase and CEA using real-time RT-PCR improves accuracy in detection of peritoneal micrometastasis of gastric cancer

Anticancer Res. 2004 Mar-Apr;24(2C):1113-20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis
  • Actins / genetics
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoembryonic Antigen / biosynthesis*
  • Carcinoembryonic Antigen / genetics
  • Cell Line, Tumor
  • False Negative Reactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peritoneal Neoplasms / diagnosis
  • Peritoneal Neoplasms / enzymology
  • Peritoneal Neoplasms / immunology
  • Peritoneal Neoplasms / secondary*
  • Phosphoric Monoester Hydrolases / biosynthesis*
  • Phosphoric Monoester Hydrolases / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods*
  • Sensitivity and Specificity
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / pathology*

Substances

  • Actins
  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • RNA, Messenger
  • Phosphoric Monoester Hydrolases
  • phosphoserine phosphatase