title: Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumours.
abstract: In previous studies we have shown down-regulation of class I major histocompatibility complex (MHC) expression in a significant proportion of primary cervical carcinomas, which was found to be strongly correlated with loss of expression of the transporter associated with antigen presentation (TAP). By contrast, class II MHC expression was frequently up-regulated on neoplastic keratinocytes in these malignancies. In order to investigate whether these changes are associated with biological behaviour of the tumours, 20 cervical carcinomas were analyzed for MHC (HLA-A, HLA-B/C, HLA-DR) and TAP-1 expression in the primary tumours and in lymph node metastases by immunohistochemistry. The results showed a significant increase in the prevalence of HLA-A and HLA-B/C down-regulation in metastasised neoplastic cells as compared with the primary 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 TAP-1 and the consequent down-regulation of class I MHC expression provides a selective advantage for neoplastic cervical cells during metastasis. Furthermore, the lack of class II MHC expression in metastasised cells either reflects a different local lymphokine production or indicates that these cells may have escaped CD4+ cytotoxic T-lymphocyte (CTL)-mediated killing.
authors.affiliation: Institute for Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: F V
authors.initials: FV
authors.lastname: Cromme
authors.forename: P F
authors.initials: PF
authors.lastname: van Bommel
authors.forename: J M
authors.initials: JM
authors.lastname: Walboomers
authors.forename: M P
authors.initials: MP
authors.lastname: Gallee
authors.forename: P L
authors.initials: PL
authors.lastname: Stern
authors.forename: P
authors.initials: P
authors.lastname: Kenemans
authors.forename: T J
authors.initials: TJ
authors.lastname: Helmerhorst
authors.forename: M J
authors.initials: MJ
authors.lastname: Stukart
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins / Q000032:analysis* / Q000096:biosynthesis; D005260:Female; D015234:HLA-A Antigens / Q000032:analysis; D015235:HLA-B Antigens / Q000032:analysis; D015236:HLA-C Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis*; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008207:Lymphatic Metastasis; D008285:Major Histocompatibility Complex; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000601:surgery
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human