Detection of K19 mRNA Compared with Tumour Markers in Peripheral Blood from Breast Cancer Patients

Objectives: A rise in peripheral blood of the glycoproteins carcino-embryonic antigen (CEA) and CA15.3 may be indicative of a subsequent clinical relapse and provides a useful adjunct in the management of metastatic breast cancer. We wished to study the relationship of these tumour markers with the expression of keratin 19 (K19) mRNA as a marker of epithelial cancer cells in periodic blood samples taken from patients undergoing postoperative therapy. Methods: CEA and CA15.3 were measured by radio-immunoassay while K19 mRNA was assessed by gel electrophoretic separation after a 40-cycle polymerase chain reaction amplification. Results: Analysis of 395 samples (regardless of patient) showed concurrence in the detection of K19 and CEA and CA15.3 (using positivity cut-offs of 3.2 ng/ml and 32 U/l, respectively) in <20% of cases that were K19+ and in >80% for samples that were K19–. The frequency of CEA and CA15.3 positivity was related to the amount of K19 product. For 65 patients with 2–3 samples collected at 6 monthly intervals, we observed complete agreement for detection of these markers (at each occasion) in about 30% of cases only. Conclusions: These discrepancies may be due partly to the currently qualitative nature of the K19 assessment and emphasize the need for quantification of this but may also reflect a difference in the source of the signals, i.e. K19 originating from circulating cells and CEA/CA15.3 shed from solid tumour deposits. It is likely that K19 detection is more sensitive, but it is less certain which of these markers reflects a significant systemic tumour load and hence is of greater value in predicting relapse.