title: c-erbB-2 and episialin challenge host immune response by HLA class I expression in human non-small-cell lung cancer.
abstract: 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.
authors.affiliation: Department of Radiotherapy/Oncology, University Hospital of Iraklion, Crete, Greece. targ@her.forthnet.gr
authors.forename: M I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: F
authors.initials: F
authors.lastname: Guddo
authors.forename: L
authors.initials: L
authors.lastname: Kaklamanis
authors.forename: M
authors.initials: M
authors.lastname: Vignola
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: H
authors.initials: H
authors.lastname: Turley
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: G
authors.initials: G
authors.lastname: Bonsignore
authors.forename: K C
authors.initials: KC
authors.lastname: Gatter
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: 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
chemical_list: D015395:Histocompatibility Antigens Class I; D018396:Mucin-1; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C116055:MUC1 tandem repeat peptide