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

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. 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 RTPCR 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. 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 RTPCR (+), including all cytology (+) patients. The optimal threshold for cycle amplification was 35, based on a receiver operating characteristic curve. CEA had the smallest deviance. 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.