Reliable and sensitive analysis of occult bone marrow metastases using automated cellular imaging

The presence of occult bone marrow metastases (OM) has been reported to rep resent an important prognostic indicator for patients with operable breast cancer and other malignancies. Assaying for OM most commonly involves labor -intensive manual microscopic analysis. The present report examines the per formance of a recently developed automated cellular image analysis system ( ACIS; ChromaVision Medical Systems, Inc) for identifying and enumerating OM in human breast cancer specimens. OM analysis was performed after immunocy tochemical staining. Specimens used in this study consisted of normal bone marrow (n = 10), bone marrow spiked with carcinoma cells (n = 20), and bone marrow obtained from breast cancer patients (n = 39). The reproducibility of ACIS-assisted analysis for tumor cell detection was examined by having a pathologist evaluate montage images generated from multiple ACIS runs of f ive specimens. Independent ACIS-assisted analysis resulted in the detection of an identical number of tumor cells for each specimen in all instrument runs. Additional studies were performed to analyze OM from 39 breast cancer patients with two pathologists performing parallel analysis using either m anual microscopy or ACIS-assisted analysis. In 17 of the 39 cases (44%), sp ecimens were classified by the pathologist as positive for tumor cells afte r ACIS-assisted analysis, whereas the same pathologist failed to identify t umor cells on the same slides after analysis by manual microscopy. These st udies indicate that the ACIS-assisted analysis provides excellent sensitivi ty and reproducibility for OM detection, relative to manual microscopy. Suc h performance may enable an improved approach for disease staging and strat ifying patients for therapeutic intervention.