c-erbB-2 and episialin challenge host immune response by HLA class I expression in human non-small-cell lung cancer.
The role of major histocompatibility complex expression in cancer prognosis and pathogenesis is contradictory. The aim of the current study was to compare the expression of HLA class I molecules and of oncoproteins that may be sources of peptides presented by HLA class I antigens in non-small-cell lung cancer. For this purpose, the expression of HLA class I antigen and TAP-1 molecule (a transporter in the antigen-processing 1 transport protein) were studied with epidermal growth factor, receptor; c-erbB-2; episialin; wild-type and mutant p53; bcl-2 oncoprotein expression; and angiogenic factor expression (vascular endothelial growth factor and thymidine phosphorylase). The degree of lymphocytic stromal infiltration and of platelet-endothelial cell adhesion molecule-expressing lymphocytes was also studied. A strong association of c-erbB-2 and MUC1 (episialin) expression with HLA class I expression was observed (p = 0.005 and 0.009, respectively). Intense CD31-positive lymphocytic infiltration was also more frequent in HLA class I-positive cases (p = 0.05). Although there was no association of HLA class I expression with survival, loss of the HLA class I expression in MUC1 or c-erbB-2 overexpressing cases conferred a poorer clinical outcome (p = 0.04). Both c-erbB-2 and MUC1 are well-known targets of T-cell-mediated cytotoxicity and cell-cell or cell-matrix adhesion-regulating proteins. The authors provide evidence that the sequence of cell adhesion-disrupting oncoprotein expression, HLA class I induction, and enhanced epitope presentation followed by lymphocytic response is an important pathogenetic three-step sequence of events that define, in part, the clinical outcome in non-small-cell lung cancer.
Koukourakis
M I
MI
Department of Radiotherapy/Oncology, University Hospital of Iraklion, Crete, Greece. targ@her.forthnet.gr
Giatromanolaki
A
A
Guddo
F
F
Kaklamanis
L
L
Vignola
M
M
Kakolyris
S
S
Turley
H
H
Georgoulias
V
V
Bonsignore
G
G
Gatter
K C
KC
Harris
A L
AL
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis / Q000276:immunology*; D010446:Peptide Fragments / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000276:immunology*; D012189:Retrospective Studies; D017741:Survivors
D015395:Histocompatibility Antigens Class I; D018396:Mucin-1; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C116055:MUC1 tandem repeat peptide