VE1 Immunohistochemistry Improves the Limit of Genotyping for Detecting BRAFV600E Mutation in Papillary Thyroid Cancer

Abstract

Detection of BRAFV600E is useful for making diagnosis and risk stratification of papillary thyroid carcinoma (PTC). Molecular testing, however, is not always available for routine clinical use. To assess the clinical utility and reliability of VE1 immunohistochemistry (IHC) for detecting BRAFV600E mutation in PTC, VE1 IHC was performed on the tissue microarrays of 514 patients with PTC and was compared with Sanger sequencing results. Of 514 PTC cases, 433 (84.2%) were positive for VE1 expression. Among 6 discordant cases between VE1 IHC and Sanger sequencing, 3 initial VE1-false negative cases turned out to be true false negative on repeat testing, and 3 VE1-false positive cases showed BRAFV600E mutation using digital PCR analysis. PTCs with low variant allele fraction were positive for VE1 IHC but were not detected using sequencing. VE1 IHC showed 99.3% sensitivity, 100% specificity, 100% positive predictive value, and 96.4% negative predictive value. The BRAFV600E mutation was significantly associated with older age, multifocality, extrathyroidal extension, lymph node metastasis, and advanced tumor stage. In conclusion, VE1 IHC is a reliable method for detecting BRAFV600E mutation in PTC specimens.

VE1 immunohistochemistry is an adjunct tool for detection of BRAFV600E mutation: Validation in thyroid cancer patients

“…The rate of BRAF V600E mutation in PTC patients mostly depends on the target population and clinicopathological characteristics, including gender, age, tumor stage, tumor focality, lymphovascular invasions, and extrathyroidal extensions 8 . The mutation is found in approximately 50% of PTC cases among western series descended from the USA 9,10 .…”

“…Several studies have been reported on the performance of VE1 IHC technique to detect the BRAF V600E mutation, and most of these reports showed exceptional concordance between this method and molecular genotyping, thus IHC can be used as an alternative method to Sanger sequencing 1,26,27 . The IHC technique consumes less time to perform multiple tests as compared to molecular methods, consequently decreasing the turnaround time 8 …”

CD73 Overexpression Promotes Progression and Recurrence of Papillary Thyroid Carcinoma

“…We enrolled 511 patients who underwent surgery for PTC from January 2008 to December 2010. The present study was performed on the same cohort used in our previous studies [ 34 , 35 , 36 , 37 ]. However, the number of patients was different because tissue loss inevitably occurs during sectioning and staining of the same archival tissue blocks.…”

“…PCR reaction was performed using BRAF exon 15-specific primers (forward 5′-TCATAATGCTTGCTCTGATAGGA-3′ and reverse 5′-GGCCAAAAATTTAATCAGTGGA-3′). Bidirectional sequencing was performed using the same primers and BigDye Terminator sequencing kit (Applied Biosystems, Foster City, CA, USA; No.4337457 on a 3730xl DNA analyzer (Applied Biosystems)), as previously described [ 34 , 36 , 40 ].…”

Prognostic Implications of CD10 and CD15 Expression in Papillary Thyroid Carcinoma

“…TNM (Tumor-Node-Metastasis) staging was done according to the 8th edition of the AJCC cancer staging manual [38]. The same data set was used in our previous studies [8,43,44], but clinical follow-up data were updated as of March 2020. All patients with total thyroidectomy took levothyroxine for suppression of thyroid-stimulating hormone (TSH).…”