Disseminated Tumor Cells in Bone Marrow of Patients with Transitional Cell Carcinoma: Immunocytochemical Detection and Correlation with Established Prognostic Indicators

Abstract

Previous investigations have demonstrated the prognostic value of disseminated cytokeratin positive cells in bone marrow of patients with breast, gastric, colon and prostate cancer. We evaluated the potential of an immunocytochemical assay, using a monoclonal antibody against cytokeratin 18 (CK 18), for the detection of disseminated tumor cells in bone marrow aspirates of patients with transitional cell carcinoma. Bone marrow aspiration was performed preoperatively on 128 patients with transitional cell carcinoma of various stages and on 27 controls with nonmalignant disease. Cytospin preparations of mononuclear bone marrow cells were incubated with a monoclonal anti-CK 18 antibody and stained using the alkaline phosphatase anti-alkaline phosphatase technique. Of the patients with transitional cell carcinoma 29.7% and none of the controls had a CK 18 positive bone marrow result. A significant correlation between the incidence of CK 18 positive cells in bone marrow and invasive transitional cell carcinoma (p <0.01), lymph node involvement (p <0.01), medium/high grade transitional cell carcinoma (p <0.01) and tumor progression in recurrent transitional cell carcinoma (p <0.05) was demonstrated. Furthermore, the mean number of CK 18 positive cells in bone marrow aspirates of patients with stage M+ and/or N+ disease was nearly 3 times as high as that of patients without clinically evident metastatic disease (10.4 versus 3.8 CK 18 positive cells per patient). A significant correlation between the incidence of CK 18 positive bone marrow results in patients with transitional cell carcinoma and established risk factors could be demonstrated in our study. Further prospective followup studies should be performed to determine the prognostic value of these findings.