ANALYSIS OF HUMAN-PAPILLOMAVIRUS INFECTION AND MOLECULAR ALTERATIONS IN ADENOCARCINOMA OF THE CERVIX

Although molecular alterations involved in the development of squamous cell carcinoma of the cervix have been extensively described, these g enetic changes have not been as well characterized in the development of cervical adenocarcinoma. Twenty-seven paraffin-embedded adenocarcin omas of the cervix, including three cases of adenoma malignum, were an alyzed for molecular alterations associated with other gynecologic mal ignancies. The presence of human papillomavirus (HPV) was assessed by polymerase chain reaction (PCR) using internally nested consensus prim ers, HPV types were identified by restriction endonuclease digestion o f the PCR products, using DNA sequencing to confirm each digestion pat tern. The presence of HPV was correlated with immunohistochemical expr ession of the p53 gene product, the presence of mutations in codon 12 of Ki-ras, and allelic deletion of markers associated with the develop ment of other gynecologic carcinomas. HPV was identified in 16 (59%) o f 27 cases, including type 18 in 7 tumors, type 16 in 7 tumors, and ty pe 45 in 2 tumors, HPV types 16 and 45 were always identified in adjac ent uninvolved cervical epithelium, but HPV type 18 was absent from th e adjacent non-neoplastic epithelium in four of the seven positive cas es. HPV was not identified in any of three cases of adenoma malignum, Diffuse immunohistochemical staining of the p53 gene product was prese nt in only one (HPV-negative) tumor, A mutation in codon 12 of Ki-ms w as observed in one endocervical adenocarcinoma (with an endometrioid p attern). Loss of heterozygosity was identified only for a marker on ch romosome 6p in one mucinous endocervical carcinoma, Most endocervical adenocarcinomas lack molecular alterations characteristic of other his tologically similar gynecologic malignancies, as well as those describ ed in cervical squamous cell carcinomas.