title: The prognostic significance of B lymphocytes in invasive carcinoma of the breast.
abstract: Although the favourable role of T lymphocyte populations in different tumour types is established, that of B cells is still a matter of debate and needs further clarification. The presence of tumour-infiltrating B cells may represent an antibody response against breast tumour antigens. We used immunohistochemistry to investigate the density and localisation of B lymphocytes infiltrating 1470 breast tumours and to identify any prognostic significance and relationship to various clinicopathological factors. Higher numbers of CD20(+) cells were found in the stroma away from the carcinoma (mean 12 cells) compared with either intratumoural or adjacent stromal compartments (mean 1 cell). The majority of tumours showed a diffuse pattern of B cells rather than aggregates. There was a positive correlation between higher numbers of total CD20(+) B cells and higher tumour grade (r (s) = 0.20, P < 0.001), ER and PgR negativity (P < 0.001), and basal phenotype (P < 0.001) subclass. In univariate survival analysis, higher total number of infiltrating CD20(+) cells, irrespective of location, was associated with significantly better BCSS (P = 0.037) and longer DFI (P = 0.001). In multivariate analysis, total CD20(+) B cell count (HR = 0.75, 95% CI = 0.58-0.96 for BCSS and HR = 0.72, 95% CI = 0.58-0.89, for DFI), tumour size, nodal stage, grade, vascular invasion, HER-2 status, and total CD8(+) T cell count were independently associated with outcome. This suggests that humoral immunity, in addition to the cell mediated immunity, may be important in breast cancer. This should be considered in breast cancer immunotherapy and vaccine strategies.
authors.affiliation: Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: S M A
authors.initials: SM
authors.lastname: Mahmoud
authors.forename: A H S
authors.initials: AH
authors.lastname: Lee
authors.forename: E C
authors.initials: EC
authors.lastname: Paish
authors.forename: R D
authors.initials: RD
authors.lastname: Macmillan
authors.forename: I O
authors.initials: IO
authors.lastname: Ellis
authors.forename: A R
authors.initials: AR
authors.lastname: Green
mesh_terms: D000328:Adult; D018951:Antigens, CD20 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004739:England; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D018951:Antigens, CD20; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone