Expression of HLA class I antigen and proteasome subunits LMP-2 and LMP-10 in primary vs. metastatic breast carcinoma lesions.
Malignant transformation of breast epithelia is frequently associated with an altered expression of MHC products and of antigen processing molecular machinery. The consequent impairment of tumor immune recognition is thought to confer to tumor cells a selective advantage with respect to survival and metastatization. In order to understand if metastatic breast cancer lesions might be associated with a defective proteasome subunit expression that, in turn, might limit the peptide availability and prevent stable cell surface HLA class I-tumor antigen expression, we studied by immunostaining the expression of beta2-microglobulin, HLA class I antigens and proteasome subunits LMP-2 and LMP-10 in 35 matched primary and metastatic human breast carcinoma lesions. Overall, we found a downregulation of LMP-2 in 51.4% of the lesions, of LPM-10 in 45.7% of the lesions, of HLA class I heavy chain in 40.0% of the lesions, while beta2-microglobulin was downregulated in 25.7% of the lesions studied. In most primary and metastatic lesions the downmodulation of each antigen examined was coordinated. In the cases where a selective downmodulation of antigens was observed in the primary or in the metastatic lesion (with the exception of beta2-microglobulin), it was rather observed in the primary lesions. However, LMP-10 showed a significant selective downmodulation in the metastases as well. Antigen downmodulation does not appear therefore to represent a strategy for the primary tumor to metastasize successfully.
Gobbi
Giuliana
G
Department of Anatomy, Pharmacology & Forensic Medicine, University of Parma, Ospedale Maggiore, Parma, Italy.
Mirandola
Prisco
P
Micheloni
Cristina
C
Solenghi
Elvira
E
Sponzilli
Ivonne
I
Artico
Marco
M
Soda
Giuseppe
G
Zanelli
Giuliana
G
Pelusi
Giuseppe
G
Fiorini
Tania
T
Cocco
Lucio
L
Vitale
Marco
M
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D015234:HLA-A Antigens / Q000096:biosynthesis*; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D008285:Major Histocompatibility Complex; D009362:Neoplasm Metastasis / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex; D001613:beta 2-Microglobulin / Q000096:biosynthesis*
D015234:HLA-A Antigens; D001613:beta 2-Microglobulin; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex