Bone marrow micrometastases and gastrointestinal cancer detection and significance

Accurate staging of cancer is important, as the presence or absence of systemic spread determines treatment. The sensitivity of current imaging and biochemical techniques is suboptimal for the detection of minimal residual disease and latent metastases. This results in understaging and potential undertreatment. To improve detection of disseminated epithelial malignancy, immunohistochemical and molecular methods have been employed that search for epithelial cell-specific proteins in nonepithelial tissue. Bone marrow is mesenchymal tissue (that does not normally express epithelial cell components) and represents an accessible window for detection of micrometastatic carcinoma cells. Detection methods for epithelial cell components (cytokeratins, epithelial membrane antigen, carcinoembryonic antigen) include immunohistochemistry, flow cytometry, reverse transcriptase polymerase chain reaction (rt-PCR), and enzyme linked immunoassay (ELISA). Micrometastatic cells in bone marrow are viable, capable of proliferation, resistant to immune attack, and insensitive to s-phase chemotherapeutic agents. Patients with carcinomas of the lung, breast, prostate, or gastrointestinal tract and in whom bone marrow micrometastases are detected have a foreshortened interval to recurrence and impaired survival. Detection of micrometastases deserves serious consideration in treatment protocols, and standardization of methods is now required.