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 oncog ene, 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 ta rget sites were selected from polymerase chain reaction (PCR) amplifie d and directly sequenced tissue sections. Tissue sections were additio nally subjected to immunohistochemical staining for p53 and WAF-1 prot ein. Because wild type p53 induces WAF-1 gene expression, immunohistoc hemical staining for WAF-1 protein using monoclonal antibodies may ser ve as an indirect means to test for p53 mutational damage. Mutational genotype was compared to histopathologic features and immunohistochemi cal staining. To study the role of HPV, L1 region consensus primers we re 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 i n each case. The virus showed no evidence of genomic variation from pr ototype HPV type 16 in the L1 segment examined. No K-ras-2 point mutat ions were identified. p53 immunopositivity was present in all tumors, being weak and focal in 4 and strong and diffuse in 1. WAF-1 immunosta ining was positive in two tumors showing weak focal p53 immunopositivi ty. The single strong and diffuse p53 immunopositive tumor was negativ e for WAF-1 and was shown to contain a missense p53 point mutation (ex on 7-codon 248 tryptophan). In conclusion, ABC is characterized by the presence of HPV type 16. K-ras-a point mutation appears to play no ro le in the development of this tumor. p53 gene alterations are common i ncluding wild type hyperexpression (weak focal p53 immunopositivity, W AF-1 positivity, no mutational change) and p53 point mutational damage .