Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants. Issue 1 (January 2014)

• Record Type: Journal Article
• Authors: Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G; Vang, Russell; Cope, Leslie; Junge, Jette; Kjaer, Susanne K; Kurman, Robert J; Shih, Ie‐Ming
• Is Part Of: Journal of pathology. Volume 232:Issue 1(2014)
• Page Start: 16
• Page End: 22
• Publication Date: 2014-01
• Subjects: Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.4293
• Languages: English
• ISSNs: 0022-3417

Abstract

<abstract abstract-type="main" id="path4293-abs-0001"> <title>Abstract</title> <p id="path4293-para-0001"> <bold>There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced‐stage disease identified from a nation‐wide tumour registry in Denmark. Mutational analysis for hotspots in <italic>KRAS</italic> and <italic>BRAF</italic> was successful in 55 APSTs and demonstrated <italic>KRAS</italic> mutations in 34 (61.8%) and <italic>BRAF</italic> mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed <italic>KRAS</italic> mutations in 34 (60.7%) and <italic>BRAF</italic> mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E <italic>BRAF</italic> mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had <italic>KRAS</italic> mutations and 14 (22%) had <italic>BRAF</italic> mutations, of which identical <italic>KRAS</italic> mutations were found in 34 (91%) of 37 SBT/APST–implant pairs and identical <italic>BRAF</italic> mutations in 14 (100%) of 14 SBT/APST–implant pairs. Wild‐type <italic>KRAS</italic> and <italic>BRAF</italic> (at the loci investigated) were found in 11 (100%) of 11 SBT/APST–implant pairs. Overall concordance of <italic>KRAS</italic> and <italic>BRAF</italic> mutations was 95% in 59 of 62 SBT/APST–implant (non‐invasive and invasive) pairs (<italic>p</italic> < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non‐invasive and invasive, harbour the identical <italic>KRAS</italic> or <italic>BRAF</italic> mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</bold> </p> </abstract>