Phänotyp minimal residualer Tumorzellen beim Mammakarzinom - Therapeutische Implikationen? Has the phenotype of minimal residual disease therapeutic implications in breast cancer?

Independent clinical studies revealed an impact of disseminated epithelial tumour cells in bone marrow on disease-free and overall survival in breast cancer. However, only a portion of the epi thelial cells is involved in the formation of solid bone metastases. Thus, a distinct cellular phenotype seems to be necessary for the metastatic growth in bone marrow. In the present study, expression of several antigens known to play a key role in the metastatic process, namely E-cadherin, EpCAM; Ki-67, EGF receptor (EGF-R), Transferrin Receptor (TR) and HLA-class I antigens, was analysed on epithelial cells in bone marrow using Alkaline-Phosphatase-Streptavidin-Immunogold double staining procedure. E-cadherin expression was detected in 15/21 (71.4 %) of the patients. In contrast to its ubiquitous expression in solid epithelial tissues the EpCAM molecule was expressed only in 6/54 patients (11.1 %) on disseminated epithelial cells in bone marrow. The three proliferation associated antigens revealed a comparable expression frequency: Ki-67 was demonstrated in 11/28 (39.3 %), EGF-R in 15/44 (34.1 %) and TR in 10/33 (30.3 %) of the patients with a positive bone marrow status. Downregula tion of HLA-class I antigens on disseminated tumour cells was found in 46.7 % of curatively resected patients without distant metastasis (R0M0, n = 30). Both, a partial (20 %) and a complete (26.7 %) loss of HLA class I antigen expression could be demonstrated. Furthermore, the HLA class I antigen negative phenotype correlated with the dedifferentiated phenotype of the primary tumour (G3; p = 0.036) and showed a tendency towards poor prognosis. We conclude that antigen profiling of disseminated tumour cells in bone marrow could lead to a better understanding of the preferential metastatic pattern of different primary tumour types. Furthermore phenotyping of these cells could identify therapeutic target structures in minimal residual disease.