KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants

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/p16(INK4a) 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
p16(INK4a) 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.