Detection of micrometastases in peritoneal washings of gastric cancer patients by the reverse transcriptase polymerase chain reaction

Gastric Cancer. 2008;11(4):206-13. doi: 10.1007/s10120-008-0483-6. Epub 2009 Jan 8.

Abstract

Background: Gastric cancer patients with positive (+) peritoneal cytology have a prognosis similar to stage IV patients. We studied the ability of quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to detect peritoneal micrometastases in patients undergoing staging laparoscopy.

Methods: Peritoneal washings were obtained prospectively from 34 patients with gastric adenocarcinoma undergoing staging laparoscopy and 6 patients undergoing laparoscopy for benign disease. Each sample underwent cytologic and RT-PCR analysis for tumor markers: carcinoembryonic antigen (CEA), cytokeratin 20 (CK20), survivin, and MUC2. Markers were evaluated on the basis of their deviance from the ideal marker.

Results: Pathologic stages for the gastric cancer patients were: stage I, 9 (27%); stage II, 7 (21%); stage III, 15 (44%); and stage IV, 3 (9%). The four cytology (+) patients were: stage II, 1; stage III, 1; and stage IV, 2. Fifteen patients were RT-PCR (+), including all cytology (+) patients. The optimal threshold for cycle amplification was 35, based on a receiver operating characteristic curve. CEA had the smallest deviance.

Conclusion: RT-PCR using a panel of tumor markers, including CEA, detects (+) cytology. The clinical significance of "false-positive" overexpression of CEA, survivin, or CK20 but cytology (-) remains to be defined. RT-PCR could represent a more sensitive method than cytology for detection of subclinical peritoneal tumor dissemination; this may be useful in improving patient selection for operative management and clinical trials.

MeSH terms

  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Carcinoembryonic Antigen / analysis
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Keratin-20 / analysis
  • Laparoscopy
  • Male
  • Microtubule-Associated Proteins / analysis
  • Middle Aged
  • Mucin-2 / analysis
  • Neoplasm Staging
  • Peritoneal Cavity / pathology*
  • Peritoneal Neoplasms / diagnosis
  • Peritoneal Neoplasms / secondary*
  • RNA, Messenger / analysis
  • ROC Curve
  • Reverse Transcriptase Polymerase Chain Reaction*
  • Stomach Neoplasms / pathology*
  • Survivin

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • Inhibitor of Apoptosis Proteins
  • Keratin-20
  • MUC2 protein, human
  • Microtubule-Associated Proteins
  • Mucin-2
  • RNA, Messenger
  • Survivin