Well-differentiated villoglandular adenocarcinoma of the uterine cervix: Oncogene/tumor suppressor gene alterations and human papillomavirus genotyping

Twelve well-differentiated villoglandular adenocarcinomas (WDVAs) of the ut erine cervix were retrospectively analyzed for the presence and specific ge notype of human papillomavirus (HPV), tumor suppressor loss (p53, MCC, APC, BRCA1), cancer gene mutation (K-ras-2, exons 1 and 2, p53 exons 5 to 8), a nd oncogene amplification (c-erbB-2/HER-2/neu, int-2). Tissue for genetic e valuation was obtained by microdissection, using 4-mu m-thick histology sec tions of archival, formalin-fixed, paraffin-embedded specimens. Genotyping involved nucleic acid amplification and DNA sequencing with gene-specific o ligonucleotides and L1 region consensus primers for common strains of HPV. Point mutation and HPV strain determination were accomplished by DNA sequen ce analysis. Tumor suppressor gene loss and oncogene amplification were per formed by allelic imbalance analysis in informative subjects based on DNA s equence and microsatellite-length polymorphisms. HPV was present in all rum ors and consisted of type 16 (n = 5, 42%) and type 18 (n = 7, 58%) strains, which have been closely associated with cervical neoplasia. K-ras-2 and p5 3 genes did not manifest point mutational damage. There was no evidence of oncogene amplification or tumor suppressor gene loss. The presence of HPV i n all 12 tumors supports the role of HPV infection in the molecular pathoge nesis of this uncommon neoplasm, The absence of associated oncogene or tumo r suppressor gene damage is consistent with indolent biological behavior an d the favorable prognosis of this unusual tumor.