Molecular Markers in Follicular and Oncocytic Thyroid Carcinomas: Clinical Application of Molecular Genetic Testing

Alicia Belaiche; Grégoire B. Morand; Sena Turkdogan; Esther ShinHyun Kang; Véronique-Isabelle Forest; Marc P. Pusztaszeri; Michael P. Hier; Alex M. Mlynarek; Keith Richardson; Nader Sadeghi; Marco A. Mascarella; Sabrina D. Da Silva; Richard J. Payne

doi:10.3390/curroncol31100441

Current Oncology (Oct 2024)

Molecular Markers in Follicular and Oncocytic Thyroid Carcinomas: Clinical Application of Molecular Genetic Testing

Alicia Belaiche,
Grégoire B. Morand,
Sena Turkdogan,
Esther ShinHyun Kang,
Véronique-Isabelle Forest,
Marc P. Pusztaszeri,
Michael P. Hier,
Alex M. Mlynarek,
Keith Richardson,
Nader Sadeghi,
Marco A. Mascarella,
Sabrina D. Da Silva,
Richard J. Payne

Affiliations

Alicia Belaiche: Faculty of Medicine, McGill University, Montreal, QC H3G 2M1, Canada
Grégoire B. Morand: Department of Otolaryngology—Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada
Sena Turkdogan: Department of Otolaryngology—Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada
Esther ShinHyun Kang: Faculty of Medicine, McGill University, Montreal, QC H3G 2M1, Canada
Véronique-Isabelle Forest: Department of Otolaryngology—Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada
Marc P. Pusztaszeri: Department of Pathology, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada
Michael P. Hier: Department of Otolaryngology—Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada
Alex M. Mlynarek: Department of Otolaryngology—Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada
Keith Richardson: Department of Otolaryngology—Head and Neck Surgery, McGill University, Royal Victoria Hospital, Montreal, QC H4A 3J1, Canada
Nader Sadeghi: Department of Otolaryngology—Head and Neck Surgery, McGill University, Royal Victoria Hospital, Montreal, QC H4A 3J1, Canada
Marco A. Mascarella: Department of Otolaryngology—Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada
Sabrina D. Da Silva: Department of Otolaryngology—Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada
Richard J. Payne: Department of Otolaryngology—Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada

DOI: https://doi.org/10.3390/curroncol31100441
Journal volume & issue: Vol. 31, no. 10
pp. 5919 – 5928

Abstract

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Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC.

Published in Current Oncology

ISSN: 1198-0052 (Print); 1718-7729 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/curroncol

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