Phänotyp minimal residualer Tumorzellen beim Mammakarzinom — Therapeutische Implikationen?

Abstract

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 epithelial 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. Downregulation 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.