MHC class I negative phenotype of disseminated tumor cells in bone marrow is associated with poor survival in R0M0 breast cancer patients

Changing the major histocompatibility complex (MHC) class I phenotype is a pivotal strategy of tumor cells to circumvent an effective immune response and is associated with tumor progression in cancer patients. Epithelial cel ls in bone marrow have been detected in various tumor types, but the clinic al observation that only a portion of the patients with a positive bone mar row status develops solid bone metastasis suggests a certain molecular equi pment of the isolated tumor cells as a prerequisite for metastatic formatio n, In the present study the prognostic impact of the MHC class I phenotype of disseminated epithelial cells in bone marrow was evaluated in a cohere o f 30 curatively resected (RO) patients without distant metastases (MO) (des ignated R0M0) who had minimal residual disease. Immunocytochemical analysis using the alkaline/anti-alkaline immunogold double staining procedure reve aled a heterogeneous MHC class I expression profile [monoclonal antibody (m Ab) W6/32] of the epithelial cells (mAb CK2), In 16 patients (53.3%) all ep ithelial cells were human leukocyte antigen (HLA) class I-positive (CK2+//W 6/32+ phenotype), Eight patients (26.7%) showed complete loss of the HLA cl ass I molecules (CK2+//W6/32- phenotype) and in 6 patients (20%) partial ro ss of HLA class I expression was found (CK2+//W6/32+ and - phenotype), CK2 cells with the HLA class I negative phenotype (CK2+//W6/32- phenotype and CK2+//W6/32+ and - phenotype) were often derived from poorly differentiated (G3) primary breast carcinomas (P = 0.036) and were associated with short survival of the R0M0 patients (follow-up 15-98 months, log rank p = 0.072), These findings support the necessity to develop immmunotherapeutic strateg ies leading to the restoration of MHC class I positive phenotype. (C) 2001 Wiley-Liss, Inc.