Bone marrow micrometastases and gastrointestinal cancer detection and significance

Accurate staging of cancer is important, as the presence or absence of syst emic spread determines treatment. The sensitivity of current imaging and bi ochemical techniques is suboptimal for the detection of minimal residual di sease and latent metastases. This results in understaging and potential und ertreatment. To improve detection of disseminated epithelial malignancy, im munohistochemical and molecular methods have been employed that search for epithelial cell-specific proteins in nonepithelial tissue. Bone marrow is m esenchymal tissue (that does not normally express epithelial cell component s) and represents an accessible window for detection of micrometastatic car cinoma cells. Detection methods for epithelial cell components (cytokeratin s, epithelial membrane antigen, carcinoembryonic antigen) include immunohis tochemistry, flow cytometry, reverse transcriptase polymerase chain reactio n (rt-PCR), and enzyme linked immunoassay (ELISA). Micrometastatic cells in bone marrow are viable, capable of proliferation, resistant to immune atta ck, and insensitive to s-phase chemotherapeutic agents. Patients with carci nomas of the lung, breast, prostate, or gastrointestinal tract and in whom bone marrow micrometastases are detected have a foreshortened interval to r ecurrence and impaired survival. Detection of micrometastases deserves seri ous consideration in treatment protocols, and standardization of methods is now required. (C) 2000 by Am. Coll. of Gastroenterology.