Tumor antigens and antigen-presenting capacity in breast cancer.
OBJECTIVE
Cancer cells frequently express antigens capable of being recognized by the host immune system; however, any resultant immune response is often ineffective. This may be related in part to tumor-induced defects in antigen presentation. We screened for dendritic cell infiltration, tumor MHC II expression and associated lymphocytic reaction in the context of three established breast tumor antigens.


METHODS
Forty primary breast tumors were evaluated by immunohistochemical techniques for expression of her2/neu, p53, and MUC1 and MHC class II molecules. Twenty-five samples were further analyzed for p53 mutations by PCR-SSCP analysis and DNA sequencing. The phenotype of tumor-infiltrating inflammatory cells was evaluated using the following markers: CD1a, MHC Class II, CD3, CD45, and CD45RO.


RESULTS
Tumors with p53 mutations and overexpression, but not her2/neu or MUC1 overexpressing tumors, more frequently harbored marked CD1a+ dendritic cell infiltrates. An overall correlation between CD1a+ cell infiltrates and HLA class II expression on tumor cells (p = 0.0008) was also observed and these tumors had greater CD45RO+ lymphocytic infiltrates.


CONCLUSIONS
In breast cancer, p53 mutations may present a more visible signal to the immune system and hence provide a better target for immunotherapy. Infiltrating CD1a positive cells are associated with a more dense tumor lymphocytic infiltrate and tumor cell expression of MHC II molecules.
McDermott
Raymond S
RS
Département d'Oncologie Médicale, Institut Curie, Paris, France. r_mcdermott@fccc.edu
Beuvon
Frédéric
F
Pauly
Marc
M
Pallud
Claude
C
Vincent-Salomon
Anne
A
Mosseri
Veronique
V
Pouillart
Pierre
P
Scholl
Susy M
SM
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000378:metabolism; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018949:Antigens, CD1; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000949:Histocompatibility Antigens Class II; D018396:Mucin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C419393:CD1a antigen