title: Usefulness of immunohistochemistry for the detection of the BRAF V600E mutation in ovarian serous borderline tumors.
abstract: Serous borderline tumors and low-grade serous adenocarcinomas typically exhibit a low mitotic index and are largely resistant to chemotherapy. They are characterized by specific mutations, including mutations of KRAS and BRAF, which target specific cell signaling pathways. Mutational analyses may provide further insight into the development sequence of low-grade serous carcinomas. There are 3 methods to detect BRAF mutations: direct sequencing, such as Sanger sequencing (Sas); immunohistochemistry (IHC); and competitive allele-specific hydrolysis probe (TaqMan) PCR technology (CAST-PCR). In the present study, we matched the results of these 3 methods in ovarian serous borderline tumor cases. This study was carried out in 11 surgically removed ovarian serous borderline tumors. Detection of the BRAF V600E mutation was carried out by the FLEX detection system using the VE1 clone antibody and the results were compared with those of Sas and CAST-PCR. The autostainer IHC VE1 assay was positive in 3 of the 11 ovarian serous borderline tumors and negative in the remaining 8 tumors. CAST-PCR demonstrated a BRAF V600E mutation ratio of 16.4, 17.7 and 12.7%, respectively, in the 3 IHC-positive cases. Sas detected the BRAF V600E mutation in only 2 cases, while revealing wild-type BRAF in the remaining 9 cases. Sas revealed KRAS mutations in 2 of these 9 cases with wild-type BRAF. Our data suggest a high concordance rate of the results between CAST-PCR and IHC. Thus, IHC using the VE1 clone and FLEX linker is a specific method for the detection of BRAF V600E and may be an alternative to molecular-biologic techniques for the detection of mutations in ovarian serous borderline tumors. This method may be a useful screening method for the BRAF mutation.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Takeshita
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City East Medical Center, Nagoya 464-8547, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Nishikawa
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arakawa
authors.affiliation: Department of Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sugiura-Ogasawara
mesh_terms: D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf