MOLECULAR-DETECTION OF CIRCULATING SOLID CARCINOMA-CELLS IN THE PERIPHERAL-BLOOD - THE CONCEPT OF EARLY SYSTEMIC-DISEASE

Detection of the mRNA of selected genes by reverse transcriptase-polym erase chain reaction (RT-PCR) is a sensitive and powerful tool for det ecting cancer cells in bone-marrow or peripheral-blood samples. In thi s study, we determined whether carcinoembryonic antigen (CEA) mRNA is detectable in the peripheral blood of patients with gastrointestinal o r breast cancer. In addition, we studied selected patients undergoing surgical procedures to assess whether tumor manipulation during operat ion enhances cancer-cell dissemination. Peripheral blood from 55 patie nts with gastrointestinal or breast cancer and from 22 control cases w as analysed for CEA mRNA using RT-PCR. For 15 selected cases undergoin g curative surgery for cancer, samples were also obtained during and a fter surgery. The lower limit of detection was 1 to 10 CEA-positive ce lls diluted among Ix10(7) blood mononuclear cells. The test was positi ve for 20 of the 55 patients with cancer (36%). None of the 22 control samples were positive. An increase in positivity was observed with in creasing stage of disease; however, even some patients with early-stag e cancer showed positive results. In addition, CEA mRNA could be detec ted in the peripheral blood during operation in 3 of 13 patients whose pre-operative CEA mRNA in the peripheral blood had been negative. The se findings suggest that, (1) RT-PCR amplification of CEA mRNA is an e fficient means of detecting circulating solid cancer cells in the peri pheral blood, although long-term clinical studies should be done to ev aluate its usefulness; (2) not only breast cancer but also gastrointes tinal cancer might be better regarded as a systemic disease even in ea rly stages of carcinoma; and (3) surgical manipulation can provoke can cer-cell dissemination. (C) 1996 Wiley-Liss, Inc.