DIFFERENCES IN MHC AND TAP-1 EXPRESSION IN CERVICAL-CANCER LYMPH-NODEMETASTASES AS COMPARED WITH THE PRIMARY TUMORS

In previous studies we have shown down-regulation of class I major his tocompatibility complex (MHC) expression in a significant proportion o f primary cervical carcinomas, which was found to be strongly correlat ed with loss of expression of the transporter associated with antigen presentation (TAP). By contrast, class II MHC expression was frequentl y up-regulated on neoplastic keratinocytes in these malignancies. In o rder to investigate whether these changes are associated with biologic al behaviour of the tumours, 20 cervical carcinomas were analysed for MHC (HLA-A, HLA-B/C, HLA-DR) and TAP-1 expression in the primary tumou rs and in lymph node metastases by immunohistochemistry. The results s howed a significant increase in the prevalence of HLA-A and HLA-B/C do wn-regulation in metastasised neoplastic cells as compared with the pr imary tumour (P = 0.01). In all cases this was accompanied by loss of TAP-1 expression. Up-regulated HLA-DR expression was found exclusively in primary tumours and was absent in the corresponding metastases (P = 0.002). These data are consistent with the hypothesis that loss of T AP-1 and the consequent down-regulation of class I MHC expression prov ides a selective advantage for neoplastic cervical cells during metast asis. Furthermore, the lack of class II MHC expression in metastasised cells either reflects a different local lymphokine production or indi cates that these cells may have escaped CD4(+) cytotoxic T-lymphocyte (CTL)-mediated killing.