LUNG-CANCER METASTATIC CELLS DETECTED IN BLOOD BY REVERSE TRANSCRIPTASE-POLYMERASE CHAIN-REACTION AND DOT-BLOT ANALYSIS

Purpose: We analayzed the blood of-patients with lung cancer at differ ent stages of presentation for the presence of carcinoembryonic antige n (CEA) mRNA detected by reverse transcriptase-polymerase chain reacti on (RT-PCR) combined with the dot-blot procedure as an indicator of mi crometastatic malignant cells. Patients and Methods: We studied 24 lun g cancer patients (10 with distant metastases and 14 with no evidence of distant metastases), eight age-and sex-marched patients affected by nonneoplastic respiratory diseases (four smokers), and eight healthy subjects, We used immunohistochemistry and RT-PCR dot-blot analysis to evaluate CEA expression in the neoplastic tissue, and the RT-PCR dot- blot procedure to analyze CEA mRNA in circulating cells. Results: The RT-PCR dot-blot procedure was highly sensitive and specific: it detect ed CEA mRNA in samples of RNA from lung cancer diluted 10(6)-fold with RNA extracted from normal blood cells, and sequence analysis confirme d that the amplified product was CEA, CEA mRNA was found in circulatin g cells from eight of 10 lung cancer patients with distant metastases (diagnostic sensitivity, 80%) and in four of 14 patients with no evide nce of distant metastases. Two of the latter had distant metastases wi thin 5 months of analysis, Thus, the diagnostic specificity of the ana lysis toward lung cancer without distant metastases was 86%, The analy sis was negative in the eight nonneoplastic patients and in the eight healthy controls. Conclusion: The RT-PCR dot-blot analysis of CFA mRNA in blood cells seems to be a promising tool for the early detection o f micrometastatic circulating cells in patients with lung cancer. (C) 1997 by American Society of Clinical Oncology.