MHC CLASS-I EXPRESSION IN HPV-16 POSITIVE CERVICAL CARCINOMAS IS POSTTRANSCRIPTIONALLY 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 po lymerase chain reaction (PCR). Localization of transcripts coding for the E7 protein was demonstrated in neoplastic cells with RNA in situ h ybridization. Consecutive tissue sections were investigated for expres sion of the major histocompatibility complex class I (MHC-I) and c-myc using immunohistochemical double staining procedures, since a role ha s 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 fr om 18 out of 23 carcinomas (78%). Varying levels of c-myc overexpressi on were observed in 12 carcinomas (52%), from which four showed positi ve MHC-I expression in c-myc overexpressing cells. In the remaining ei ght 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 neopla stic cells that show negative staining for MHC-I protein. These data s trongly indicate that MHC-I down-regulation in cervical carcinomas inv olves post-transcriptional mechanisms, not directly related to E7 tran scription and overexpression of c-myc.