MHC class I expression in HPV 16 positive cervical carcinomas is post-transcriptionally controlled and independent from c-myc overexpression.
Squamous cell carcinomas of the uterine cervix (n = 23) were selected for the presence of human papillomavirus type 16 (HPV 16) using the polymerase chain reaction (PCR). Localization of transcripts coding for the E7 protein was demonstrated in neoplastic cells with RNA in situ hybridization. Consecutive tissue sections were investigated for expression of the major histocompatibility complex class I (MHC-I) and c-myc using immunohistochemical double staining procedures, since a role has been suggested for the c-myc protein in MHC-I down-regulation and c-myc overexpression has been described in cervical carcinomas. Reduced expression of class I heavy chains was observed in neoplastic cells from 18 out of 23 carcinomas (78%). Varying levels of c-myc overexpression were observed in 12 carcinomas (52%), from which four showed positive MHC-I expression in c-myc overexpressing cells. In the remaining eight c-myc overexpressing carcinomas MHC-I down-regulation was observed. Additional RNA in situ hybridization with class I heavy chain locus-specific RNA-probes revealed presence of class I mRNAs in those neoplastic cells that show negative staining for MHC-I protein. These data strongly indicate that MHC-I down-regulation in cervical carcinomas involves post-transcriptional mechanisms, not directly related to E7 transcription and overexpression of c-myc.
Cromme
F V
FV
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Snijders
P J
PJ
van den Brule
A J
AJ
Kenemans
P
P
Meijer
C J
CJ
Walboomers
J M
JM
D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000382:microbiology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D016259:Genes, myc; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000302:isolation & purification*; D050725:Papillomavirus E7 Proteins; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000382:microbiology
D004279:DNA, Viral; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16