The Impact of 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
Author Information
Mawaddah Abdulhaleem: Department of Otolaryngology-Head and Neck Surgery, McGill University, Royal Victoria Hospital, Montreal, QC H4A 3J1, Canada. ORCID
Marc Philippe Pusztaszeri: Department of Pathology, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada. ORCID
Mohannad Rajab: Department of Otolaryngology-Head and Neck Surgery, King Faisal Specialist Hospital & Research Center, Al Madinah Al Munawwarah 42523, Saudi Arabia.
Hannah Greenspoon: Faculty of Arts and Science, Queen's University, Kingston, ON K7L 3N6, Canada.
Joshua Ross Krasner: Faculty of Medicine, Israel Institute of Technology, Haifa 3200003, Israel.
Sabrina Daniela Da Silva: Department of Otolaryngology-Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Véronique-Isabelle Forest: Department of Otolaryngology-Head and Neck Surgery, McGill University, Royal Victoria Hospital, Montreal, QC H4A 3J1, Canada.
Richard J Payne: Department of Otolaryngology-Head and Neck Surgery, McGill University, Royal Victoria Hospital, Montreal, QC H4A 3J1, Canada.
BACKGROUND: A mutation in papillary Thyroid Cancer (PTC) has been shown to be associated with aggressive behavior. Nevertheless, not all 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 AF and the histopathological features of thyroid malignancies is not well understood. We hypothesized that the 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 thyroid malignancies from 2019 to 2022 at McGill University tertiary care hospitals ( = 317). patients with -positive malignancies that included information on AF were included ( = 44). The correlation between AF and tumor histopathological features was analyzed. RESULTS: Out of the 44 nodules with a 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% ( = 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%) ( = 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 ( = 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 ( = 0.160). CONCLUSION: In this study, 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.
