Virchows Archiv

, Volume 465, Issue 2, pp 193–198 | Cite as

Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma

  • Gian Franco Zannoni
  • Giuseppina Improta
  • Gaia Chiarello
  • Angela Pettinato
  • Marco Petrillo
  • Paolo Scollo
  • Giovanni Scambia
  • Filippo Fraggetta
Original Article


Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer with characteristic biological features and aggressive clinical behavior. OCCCs show a pattern of gene mutations different from other type I ovarian malignancies, notably a higher frequency of PIK3CA mutations. In low grade serous ovarian cancer, KRAS and BRAF mutations are frequent, but little data are available on the mutational status of these genes in OCCCs. To clarify this issue, we designed a clinicopathological study with the aim to establish the incidence of KRAS, NRAS, and BRAF hot spot mutations in OCCC. Between December 2006 and June 2012, 22 patients with a proven diagnosis of OCCC were admitted to our Institutions. In all cases, final diagnosis was established according to FIGO and WHO criteria. All women received complete surgical staging. The PyroMark Q24 system (Qiagen GmbH, Hilden, Germany) was used for pyrosequencing analysis of KRAS, NRAS, and BRAF hot spot regions on 2.5-μm sections of formalin-fixed paraffin-embedded tissue from primary OCCC. Pyrosequencing analysis of KRAS, NRAS, and BRAF hot spot regions revealed the presence of mutations only at codon 12 in exon 2 of KRAS in 3 of 22 (14 %) cases. We found no mutations in the hot spot regions of NRAF (exons 2, 3, 4) or BRAF (exon 15). The median age of women with a KRAS mutated OCCC was 74 years. These OCCC were unilateral FIGO stage IA lesions in two cases associated with foci of endometriosis. We conclude that in 14 % of OCCCs, a KRAS mutation occurs in codon 2 exon 2. NRAS and BRAF mutations were not found.


Clear-cell ovarian carcinoma KRAS NRAS BRAF Hot spot mutations 


Conflict of interest

We declare that we have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Gian Franco Zannoni
    • 1
  • Giuseppina Improta
    • 2
  • Gaia Chiarello
    • 1
  • Angela Pettinato
    • 3
  • Marco Petrillo
    • 4
  • Paolo Scollo
    • 5
  • Giovanni Scambia
    • 4
  • Filippo Fraggetta
    • 3
  1. 1.Department of PathologyCatholic University of the Sacred HeartRomeItaly
  2. 2.Laboratory of Clinical Research and Advanced DiagnosticsIRCCS-CROB HospitalPotenzaItaly
  3. 3.Department of PathologyOspedale CannizzaroCataniaItaly
  4. 4.Department of Obstetrics and GynecologyCatholic University of the Sacred HeartRomeItaly
  5. 5.Department of Obstetrics and GynecologyOspedale CannizzaroCataniaItaly

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