Identification of Primary Tumor Markers in Occult Bone Marrow Micrometastasis.

Abstract : Our earlier results showed that the presence of cytokeratin positive epithelial cells in the bone marrow is an independent predictor of worse prognosis in human breast cancer. The biological origin and the cellular and molecular characteristics of these cells in not known and was the objective of the present proposal. We have characterized a set of 47 primary breast cancers with respect to expression of mutant p53 and HSP27. Our results are consistent with the findings that expression of mutant p53 is associated with metastatic spread be it occult as found in bone marrow or positive lymph nodes. 57% of pS3 eve tumors were associated with bone marrow micrometastasis (BMM) as compared to 15% of p53 -ve tumors with BMM positive. We have developed a novel culture technique that can be adapted to separate the epithelial cancer cells in the bone marrow. This will allow us to fully characterize these cells at the cellular and molecular level and define their origin, thus fulfilling the major objective of this proposal.