title: KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants.
abstract: BACKGROUND
  Patients diagnosed for a serous ovarian borderline tumor (s-BOT) typically present with an excellent clinical outcome. However there have been controversies concerning the prognostic impact of so-called implants, an extra ovarian spread occurring alongside the s-BOT in certain cases. It remains obscure whether these implants actually resemble metastasis owning the same genetic pattern as the ovarian primary or whether they develop independently.
  
  
  METHODS
  The current study, in the aim of further clarifying the genetic origin of implants, assessed BRAF/KRAS hot spot mutations and the p53/p16INK4a immunophenotype of s-BOTs and corresponding implants (n=49) of 15 patients by pyro-sequencing and immunostaining, respectively.
  
  
  RESULTS
  A significant proportion of both s-BOTs and implants showed KRAS or BRAF mutation and though p16INK4a was found to be abundantly expressed, p53 immunoreactivity was rather low. When genotypes of BRAF/KRAS mutated s-BOTs and corresponding implants were compared no patient presented with a fully matching mutation profile of s-BOTs and all corresponding implants.
  
  
  CONCLUSIONS
  The current study reveals genetic heterogeneity of s-BOTs and implants, as none of the markers examined showed constant reciprocity. Hence, our findings may assist to explain the different clinical presentation of s-BOTs and implants and might encourage to applying more individualized follow up protocols.
authors.forename: Sabine
authors.initials: S
authors.lastname: Heublein
authors.forename: Katinka
authors.initials: K
authors.lastname: Grasse
authors.forename: Harald
authors.initials: H
authors.lastname: Hessel
authors.forename: Alexander
authors.initials: A
authors.lastname: Burges
authors.forename: Miriam
authors.initials: M
authors.lastname: Lenhard
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
authors.affiliation: Department of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany. doris.mayr@med.uni-muenchen.de.
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
mesh_terms: D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology*; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins