BRAF Mutation-Associated Immunostaining Marker and Morphological Features in Peritoneal Implants and Atypical Proliferative (Borderline) Serous Tumors (APSTs)
Laura Ardighieri, Robert J Kurman, Kruti Maniar, Ie-Ming Shih. Johns Hopkins University School of Medicine, Baltimore, MD
Background: Peritoneal implants associated with atypical proliferative (borderline) serous tumors (APSTs) represent a clinically and biologically intriguing group of lesions. While exome sequencing analysis has identified KRAS/BRAF mutations as the main genetic alterations in APSTs, the molecular nature of peritoneal implants remain largely elusive, mostly because their minute size and contamination of stromal cells challenge any molecular characterization. The VE1 antibody is a recently developed monoclonal antibody that recognizes the epitope generated by the V600E mutation in BRAF. In this study, we took advantage of VE1 immunoreactivity as a surrogate marker for BRAF V600E mutation to study the BRAF mutation status in those lesions that had sufficient DNA for mutation analysis.
Design: VE1 immunohistochemistry was performed in a group of 33 APSTs and 27 peritoneal implants. BRAF and KRAS mutational status was determined in all APSTs and in 19 peritoneal implants specimens which had enough genomic material to perform mutational analysis. Their mutation status was then correlated with the VE1 staining. In this study, we further identified the morphological features that were enriched in those specimens with BRAF V600E mutation.
Results: By analyzing 33 APSTs (including 20 cases with BRAF V600E) and 19 peritoneal implants (including 12 lesions with BRAF V600E), we were able to demonstrate 100% sensitivity and 100% specificity by applying VE1 immunoreactivity in detecting BRAF V600E. Moreover, we detected VE1 immunoreactivity in additional 7 implants that were too small to perform mutational analysis. By correlating molecular and morphological findings, we found certain morphological features in tumors that harbored BRAF V600E. Those features included 1) the presence of the “senescence-like” cells exhibiting round or polygonal shape with abundant eosinophilic cytoplasm and degenerating nuclei, 2) “budding” from the APST epithelial monolayer and 3) individual cells or poorly cohesive aggregates in the peritoneal implants.
Conclusions: Our data strongly suggest that VE1 immunoreactivity is the surrogate marker for BRAF V600E in APST and associated implants. The morphological features that are frequently observed in BRAF mutated samples are helpful in distinguishing APSTs and related implants with BRAFV600E mutations from those without. Both immunostaining and morphological features can be readily applied to study APSTs and their related implants in paraffin tissues including those that are minute in size.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 164, Wednesday Morning