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 com pare the expression of HLA class I molecules and of oncoproteins that may b e sources of peptides presented by HLA class I antigens in non-small-cell l ung cancer. For this purpose, the expression of HLA class I antigen and TAP -1 molecule (a transporter in the antigen-processing 1 transport protein) w ere studied with epidermal growth factor, receptor; c-erbB-2; episialin; wi ld 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-endotheli al cell adhesion molecule-expressing lymphocytes was also studied. A strong association of c-erbB-2 and MUC1 (episialin) expression with HLA class I e xpression was observed (p = 0.005 and 0.009, respectively). Intense CD31-po sitive lymphocytic infiltration was also more frequent in HLA class I-posit ive cases (p = 0.05). Although there was no association of HLA class I expr ession 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 a nd cell-cell or cell-matrix adhesion-regulating proteins. The authors provi de evidence that the sequence of cell adhesion-disrupting oncoprotein expre ssion, HLA class I induction, and enhanced epitope presentation followed by lymphocytic response is an important pathogenetic three-step sequence of e vents that define, in part, the clinical outcome in non-small-cell lung can cer.