Microsatellite Marker Polymorphisms Provide Evidence for Germ Cell Origin of Mucinous Ovarian Carcinomas Associated with Concurrent Teratomas.
Sarah E Kerr, Matthew J McFalls, Ariel B Flotte, Kevin C Halling, Debra A Bell. Mayo Clinic, Rochester, MN
Background: Two decades ago, careful studies of chromosomal heteromorphisms and DNA polymorphisms proved that ovarian teratomas are derived from the female host during gametogenesis. When the teratoma arises during meiosis I, chromosomal recombination events result in partial homozygosity in multiple chromosomes. When the teratoma arises during meiosis II, a haploid gamete can either endoreduplicate (resulting in complete homozygosity), or fuse with another haploid gamete (resulting in partial homozygosity). We sought to use these concepts to prove that mucinous carcinomas associated with ovarian teratomas are also germ cell derived.
Design: Six cases of mucinous carcinoma associated with ovarian teratomas were identified. DNA was extracted separately from the teratoma, mucinous carcinoma, and normal tissue after scalpel dissection of tissues from unstained formalin fixed, paraffin embedded sections. Twelve polymorphic microsatellite markers were PCR amplified for each sample; the resulting fluorescently labeled fragments were measured by capillary electrophoresis. Alleles from the teratomas and carcinomas were scored for each marker as non-informative (normal tissue homozygous or PCR failure), heterozygous (two alleles present), or homozygous (one allele present in tumor when normal tissue heterozygous).
Results: Three cases of mucinous carcinoma showed near complete/complete homozygosity for informative markers (8/9, 9/9, and 10/10, respectively). Two of these had identically homozygous teratomas (the third teratoma was unavailable for analysis). Two carcinoma/teratoma pairs were completely heterozygous for all 8 informative markers. The remaining case had a teratoma homozygous for 2 of 10 informative markers, while the matching carcinoma was definitively homozygous for only one of these markers.
Conclusions: Microsatellite polymorphism analysis demonstrates that mucinous ovarian carcinomas genetically match associated teratomas when present. Although this technique does not unequivocally distinguish between homozygosity and loss of heterozygosity (hemizygosity) in the carcinomas, presumed homozygosity across multiple markers in 3 of 6 cases is strong evidence that some mucinous carcinoma/teratoma pairs arise from an endoreduplicated haploid gamete during meiosis II. Similar testing of a larger set of mucinous ovarian carcinomas may show that a subset of mucinous carcinomas have obliterated a pre-existing teratoma and are germ cell (rather than epithelial) derived.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 145, Monday Morning