Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA: Longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers

The use of reverse transcription-PCR (RT-PCR) to analyze cells in the blood of cancer patients for the detection of mRNA expressed in tumor cells has implications for both the prognosis and the monitoring of cancer patients f or the efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA) is expressed on similar to 95% of colorectal, gastric, and pa ncreatic tumors, and on the majority of breast, non-small cell lung, and he ad and neck carcinomas. CEA shed in serum is useful as a marker in only sim ilar to 50% of colorectal cancer patients and rarely is shed by some other carcinoma types, RT-PCR has been used previously to detect CEA mRNA in cell s in the blood and lymph nodes of cancer patients, Under the assay conditio ns validated in the studies reported here, 34 of 51 (67%) patients with dif ferent stages of colorectal cancer had blood cells that were positive by RT -PCR for CEA mRNA, whereas none of 18 patients with colonic polyps were pos itive; 2 of 60 apparently healthy individuals (who were age and sex matched with the carcinoma patients and were part of a colon cancer screening prog ram as controls) were marginally positive. The results of CEA PCR in the bl ood of the carcinoma patients and the other groups showed strong statistica l correlation with the disease (P2 < 0.0001). Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in blood cells of colorec tal carcinoma patients by RT-PCR, For all stages of disease, 18 of 51 patie nts (35%) were positive for serum CEA, whereas 35 of 51 (69%) were positive by RT-PCR. More importantly, only 5 of 23 (20%) of stage B and C colorecta l cancer patients were positive for serum CEA, whereas 16 of 23 (70%) were positive by RT-PCR, The use of two other serum markers (CA19.9 and CA72-4) for colorectal cancer in combination with serum CEA scored two additional p atients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long- term longitudinal studies conducted before and after surgery identified som e patients with CEA mRNA in blood cells that were negative for all serum ma rkers, who eventually developed clinical metastatic disease, The studies re ported here are the first to correlate RT-PCR results for CFA mRNA in blood cells with one or more serum markers for patients with different stages of colorectal cancer, and are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in blood cells of cancer patients, Larger cohort s will be required in future studies to define the impact, if any, of this technology on prognosis and/or disease monitoring,