The origin and molecular characterization of adenoid basal carcinoma of the uterine cervix.

Five cases of adenoid basal carcinoma (ABC) of the uterine cervix were examined for the presence of p53 tumor suppressor gene, K-ras-2 oncogene, and human papillomavirus (HPV). A topographic genotyping approach was used to search for point mutations in K-ras-2 (exon 1 and 2) and p53 (exons 5 to 8) in archival formalin-fixed tissue blocks. Minute target sites were selected from polymerase chain reaction (PCR) amplified and directly sequenced tissue sections. Tissue sections were additionally subjected to immunohistochemical staining for p53 and WAF-1 protein. Because wild type p53 induces WAF-1 gene expression, immunohistochemical staining for WAF-1 protein using monoclonal antibodies may serve as an indirect means to test for p53 mutational damage. Mutational genotype was compared to histopathologic features and immunohistochemical staining. To study the role of HPV, L1 region consensus primers were used to amplify topographic samples, followed by HPV genotyping by direct sequencing and comparison to known viral strains. ABC was found to contain HPV in all cases, proven by genotyping to be HPV type 16 in each case. The virus showed no evidence of genomic variation from prototype HPV type 16 in the L1 segment examined. No K-ras-2 point mutations were identified. p53 immunopositivity was present in all tumors, being weak and focal in 4 and strong and diffuse in 1. WAF-1 immunostaining was positive in two tumors showing weak focal p53 immunopositivity. The single strong and diffuse p53 immunopositive tumor was negative for WAF-1 and was shown to contain a missense p53 point mutation (exon 7-codon 248 tryptophan). In conclusion, ABC is characterized by the presence of HPV type 16. K-ras-2 point mutation appears to play no role in the development of this tumor. p53 gene alterations are common including wild type hyperexpression (weak focal p53 immunopositivity, WAF-1 positivity, no mutational change) and p53 point mutational damage.