Clinical evaluation of a panel of mRNA markers in the detection of disseminated tumor cells in patients with operable breast cancer.

Persistent high mortality rates in breast cancer patients, in spite of latest advances in diagnosis and therapy, affirm the necessity of new developments in tumor biology prognostic factors. Immunocytochemical detection of disseminated breast cancer cells in bone marrow has been frequently associated with a decrease in disease-free survival as an independent prognostic factor, but methods based on molecular biology procedures must still be validated. Considering tumor heterogeneity, the multimarker approach has been suggested as a better strategy than individual marker assays. The aim of this work was evaluation of the prognostic value of a multimarker reverse-transcriptase polymerase chain reaction (RT-PCR) assay, associating four mRNA markers for the detection of disseminated breast cancer cells. We compared the prognostic significance of cytokeratin 19 (CK19), carcinoembryonic antigen (CEA), mammaglobin (MG) and the mucin MUC5B mRNA in bone marrow aspirates in the follow-up of 80 operable breast cancer patients. The best prognostic value for clinical outcome was seen for CEA mRNA, not improved for any association with other markers. Unexpectedly, some tumor mRNA in bone marrow correlates with a favorable clinical outcome, especially MUC5B. Therefore, our results suggest that not all epithelial or tumor markers have the same significance in predicting the metastatic potential of disseminated cancer cells. New parameters are needed for the identification of individual patients at high risk of tumor recurrence. Multimarker RT-PCR assays could be a good approach, but they should be performed associating mRNA markers that are able to predict tumor aggressiveness associated with poor outcome and not just epithelial markers, which only indicate the mere presence of tumor cells.