title: MHC class I negative phenotype of disseminated tumor cells in bone marrow is associated with poor survival in R0M0 breast cancer patients.
abstract: 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 cells in bone marrow have been detected in various tumor types, but the clinical observation that only a portion of the patients with a positive bone marrow status develops solid bone metastasis suggests a certain molecular equipment of the isolated tumor cells as a prerequisite for metastatic formation. In the present study the prognostic impact of the MHC class I phenotype of disseminated epithelial cells in bone marrow was evaluated in a cohort of 30 curatively resected (R0) patients without distant metastases (M0) (designated R0M0) who had minimal residual disease. Immunocytochemical analysis using the alkaline/anti-alkaline immunogold double staining procedure revealed a heterogeneous MHC class I expression profile [monoclonal antibody (mAb) W6/32] of the epithelial cells (mAb CK2). In 16 patients (53.3%) all epithelial cells were human leukocyte antigen (HLA) class I-positive (CK2+//W6/32+ phenotype). Eight patients (26.7%) showed complete loss of the HLA class I molecules (CK2+//W6/32- phenotype) and in 6 patients (20%) partial loss 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 strategies leading to the restoration of MHC class I positive phenotype.
authors.affiliation: Klinikum Grosshadern, Department of Surgery, Ludwig-Maximilians University, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Zia
authors.forename: F W
authors.initials: FW
authors.lastname: Schildberg
authors.forename: I
authors.initials: I
authors.lastname: Funke
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007633:Keratins / Q000276:immunology; D008875:Middle Aged; D018365:Neoplasm, Residual; D010641:Phenotype; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007633:Keratins