The ribosomal P0 protein induces a spontaneous immune response in patients with head and neck advanced stage carcinoma that is not dependent on its overexpression in carcinomas.
A typical feature in systemic lupus erythemathosus patients is the presence of autoantibodies to the carboxyl-terminal homologous P proteins (P0, P1, P2) domain (C-22 P0 epitope). In this report we provide evidence for the in vivo immunogenicity of the P0 protein in head and neck cancer patients as well as overexpression by immunohistochemistry of the C-22 P0 epitope in invasive carcinomas (55/57). Overexpression of this epitope was also significantly associated with a number of pathological lesions arising in the head and neck stratified epithelium including acanthosis (8/8), benign tumors (11/11), dysplasia (23/25) and in situ carcinomas (9/9). Intermediate cell layer restricted epitope overexpression was observed in well differentiated carcinomas, while undifferentiated tumors showed overexpression throughout the cell layers. Employing recombinant P proteins, sera from 40 of the 57 carcinoma patients and 39 normal donors, were subjected to immunoblot analysis. Immunity to P0 protein (7/40) was associated with malignancy and with advanced disease stage, but it was not dependent on the C-22 P0 epitope overexpression, although it was the preferential autoantibody target in 4 patients. Increased expression of the C-22 P0 epitope on the surface of pharynx cancer cells following cellular stress in vitro, may imply P0 protein presentation as an in vivo autoantibody target in cancer patients. Evidence for immunity to the P0 protein, as well as overexpression in patients with head and neck carcinoma may be relevant for monitoring cancer progression, in planning immunotherapeutic strategies, and contribute to the understanding of immuno-biological behaviour of head and neck carcinomas.
Bei
Roberto
R
Department of Experimental Medicine and Biochemical Sciences, University Tor Vergata, I-00133, Rome, Italy. bei@med.uniroma2.it
Masuelli
Laura
L
Trono
Paola
P
Orvietani
Pier Luigi
PL
Losito
Simona
S
Marzocchella
Laura
L
Vitolo
Domenico
D
Albonici
Loredana
L
Mrozek
Marie-Agnes
MA
Di Gennaro
Elena
E
Lista
Florigio
F
Faggioni
Giovanni
G
Ionna
Franco
F
Binaglia
Luciano
L
Manzari
Vittorio
V
Budillon
Alfredo
A
Modesti
Andrea
A
D000595:Amino Acid Sequence; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D000939:Epitopes; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D012269:Ribosomal Proteins / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D012269:Ribosomal Proteins; C054675:ribosomal protein P0