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 uterine cervix were retrospectively analyzed for the presence and specific genotype 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), and oncogene amplification (c-erbB-2/HER-2/neu, int-2). Tissue for genetic evaluation was obtained by microdissection, using 4-micron-thick histology sections of archival, formalin-fixed, paraffin-embedded specimens. Genotyping involved nucleic acid amplification and DNA sequencing with gene-specific oligonucleotides and L1 region consensus primers for common strains of HPV. Point mutation and HPV strain determination were accomplished by DNA sequence analysis. Tumor suppressor gene loss and oncogene amplification were performed by allelic imbalance analysis in informative subjects based on DNA sequence and microsatellite-length polymorphisms. HPV was present in all tumors 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 p53 genes did not manifest point mutational damage. There was no evidence of oncogene amplification or tumor suppressor gene loss. The presence of HPV in all 12 tumors supports the role of HPV infection in the molecular pathogenesis of this uncommon neoplasm. The absence of associated oncogene or tumor suppressor gene damage is consistent with indolent biological behavior and the favorable prognosis of this unusual tumor.
Jones
M W
MW
Department of Pathology, Magee-Womens Hospital, University of Pittsburgh, PA 15213, USA.
Kounelis
S
S
Papadaki
H
H
Bakker
A
A
Swalsky
P A
PA
Woods
J
J
Finkelstein
S D
SD
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D000328:Adult; D004279:DNA, Viral / Q000032:analysis / Q000737:chemistry; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009857:Oncogenes / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears
D004279:DNA, Viral