Open Access Research article

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

Sabine Heublein1, Katinka Grasse2, Harald Hessel2, Alexander Burges3, Miriam Lenhard3, Jutta Engel4, Thomas Kirchner2, Udo Jeschke1 and Doris Mayr2*

Author Affiliations

1 Department of Gynecology and Obstetrics, Ludwig-Maximilians-University of Munich-Campus Innenstadt, Munich, Germany

2 Department of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany

3 Department of Gynecology and Obstetrics, Ludwig-Maximilians-University of Munich-Campus Grosshadern, Munich, Germany

4 Department of Biostatistics and Epidemiology, Munich Tumor Registry, Ludwig-Maximilians-University of Munich, Munich, Germany

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BMC Cancer 2013, 13:483  doi:10.1186/1471-2407-13-483

Published: 18 October 2013

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 (nā€‰=ā€‰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.

Keywords:
KRAS; BRAF; Serous ovarian borderline tumor; Implants