Prediction of peritoneal micrometastasis by peritoneal lavaged cytology and reverse transcriptase-polymerase chain reaction for matrix metalloproteinase-7 mRNA.

PURPOSE: Peritoneal dissemination is the most common cause of death associated with gastric cancer. In this study, we report the significance of molecular diagnosis of peritoneal dissemination by means of matrix metalloproteinase-7 (MMP-7) reverse transcriptase-PCR (RT-PCR) assay using preoperative peritoneal wash fluid.

EXPERIMENTAL

DESIGN

Preoperative peritoneal lavage by paracentesis was performed on 152 patients with gastric cancer. The peritoneal lavaged fluid was subjected to RT-PCR analysis with primers specific for MMP-7 and conventional cytological Papanicolaou examination.

RESULTS

The MMP-7 RT-PCR assay was able to detect cancer cells at densities even lower than 10 cells/sample. There was no signal of MMP-7 mRNA from mesothelial cells, fibroblasts, peripheral blood, and lavaged fluid from patients with benign disease. Cytological examination and MMP-7 RT-PCR assay results were positive for 27 (18%) and 28 (18%) samples, respectively. The sensitivity for the prediction of peritoneal dissemination by cytology and MMP-7 RT-PCR assay were 46% and 33%, but the combination analysis using both parameters improved the sensitivity rate with 62%. Logistic regression analysis revealed that the cytological examination and MMP-7 RT-PCR assay are independent predictors of peritoneal dissemination.

CONCLUSION

The combination of cytological examination and RT-PCR assay of preoperative peritoneal lavaged fluid is a highly efficient and reliable method for the selection of patients for adjuvant i.p. chemotherapy.