The Impact of BRAF V600E Mutation Allele Frequency on the Histopathological Characteristics of Thyroid Cancer

Mawaddah Abdulhaleem; Saruchi Bandargal; Marc Philippe Pusztaszeri; Mohannad Rajab; Hannah Greenspoon; Joshua Ross Krasner; Sabrina Daniela Da Silva; Véronique-Isabelle Forest; Richard J Payne

doi:10.3390/cancers16010113

The Impact of BRAF V600E Mutation Allele Frequency on the Histopathological Characteristics of Thyroid Cancer

Cancers (Basel). 2023 Dec 25;16(1):113. doi: 10.3390/cancers16010113.

Authors

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, McGill University, Royal Victoria Hospital, Montreal, QC H4A 3J1, Canada.
² Department of Otolaryngology-Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
³ Faculty of Medicine, McGill University, Montreal, QC H3G 2M1, Canada.
⁴ Department of Pathology, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
⁵ Department of Otolaryngology-Head and Neck Surgery, King Faisal Specialist Hospital & Research Center, Al Madinah Al Munawwarah 42523, Saudi Arabia.
⁶ Faculty of Arts and Science, Queen's University, Kingston, ON K7L 3N6, Canada.
⁷ Faculty of Medicine, Israel Institute of Technology, Haifa 3200003, Israel.

Abstract

Background: A BRAF V600E mutation in papillary thyroid cancer (PTC) has been shown to be associated with aggressive behavior. Nevertheless, not all BRAF V600E PTCs behave aggressively. Allele frequency (AF) is the number of mutated molecules divided by the total number of wild-type molecules at a specific location in the genome. The relationship between BRAF V600E AF and the histopathological features of thyroid malignancies is not well understood. We hypothesized that the BRAF V600E AF will correlate directly with aggressive histopathological behavior. The aim of this study was to examine this relationship.

Methods: A retrospective chart review was performed for patients treated for BRAF V600E thyroid malignancies from 2019 to 2022 at McGill University tertiary care hospitals (n = 317). Patients with BRAF V600E-positive malignancies that included information on AF were included (n = 44). The correlation between AF and tumor histopathological features was analyzed.

Results: Out of the 44 nodules with a BRAF V600E mutation, those with aggressive features of PTC had a mean AF of 25.8%, which was significantly higher than the non-aggressive group with a mean AF of 10.25% (p = 0.020). Additionally, there was a statistically significant difference in mean AF between patients with a positive sentinel LN (29%) and those with a negative sentinel LN (17.8%) (p = 0.021). Classical PTC was present in 29.5% (13/44) of nodules, with a mean AF of 15.6%. The tall cell subtype was found in 64% (28/44) of nodules, with a mean AF of 23%. Solid and hobnail subtypes were less common in this study, and there was no statistically significant relationship between AF and histopathological subtypes (p = 0.107). Nodules smaller than 1cm had a mean AF of 13.3%, while nodules ranging from 1 2cm had a mean AF of 20.6%, and those larger than 2cm had a mean AF of 27.7%. However, no statistical difference was observed between AF and nodule size (p = 0.160).

Conclusion: In this study, BRAF V600E mutations in conjunction with AF help to determine whether thyroid malignancies will display aggressive behavior. This pre-operative finding can help thyroid specialists to determine the extent of thyroidectomy and whether lymph node dissection is required.

Keywords: BRAF V600E; allele frequency; molecular mutations; molecular testing; thyroid cancer.

Grants and funding

This research received no external funding.