AUTHOR=Khonrak Thitima , Watcharadetwittaya Sasithorn , Chamgramol Yaovalux , Intarawichian Piyapharom , Deenonpoe Raksawan 

TITLE=RET rearrangements are relevant to histopathologic subtypes and clinicopathological features in Thai papillary thyroid carcinoma patients

JOURNAL=Pathology and Oncology Research

VOLUME=29

YEAR=2023

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2023.1611138

DOI=10.3389/pore.2023.1611138

ISSN=1532-2807

ABSTRACT=<p><bold>Background:</bold> Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer<italic>.</italic> The <italic>RET</italic> gene rearrangements <italic>CCDC6</italic>::<italic>RET</italic> and <italic>NCOA4</italic>::<italic>RET</italic> are the most common <italic>RET</italic> gene rearrangements in PTC patients. Different <italic>RET</italic>::<italic>PTC</italic> rearrangements are associated with different PTC phenotypes.</p><p><bold>Methods:</bold> Eighty-three formalin-fixed paraffin-embedded (FFPE) PTC samples were examined. The prevalence and expression levels of <italic>CCDC6</italic>::<italic>RET</italic> and <italic>NCOA4</italic>::<italic>RET</italic> were determined using semi-quantitative polymerase chain reaction (qRT-PCR). The association of these rearrangements with clinicopathological data was investigated.</p><p><bold>Results:</bold> The presence of <italic>CCDC6</italic>::<italic>RET</italic> rearrangement was significantly associated with the classic subtype and absence of angio/lymphatic invasion (<italic>p</italic> &lt; 0.05). While <italic>NCOA4</italic>::<italic>RET</italic> was associated with the tall-cell subtype, and presence of angio/lymphatic invasion and lymph node metastasis (<italic>p</italic> &lt; 0.05). Multivariate analysis demonstrated that an absence of extrathyroidal extension and extranodal extension were independent predictive factors for <italic>CCDC6</italic>::<italic>RET</italic>, whereas the tall-cell subtype, large tumor size, angioinvasion, lymphatic invasion and perineural invasion were independent predictive factors for <italic>NCOA4</italic>::<italic>RET</italic> (<italic>p</italic> &lt; 0.05). However, the mRNA expression level of <italic>CCDC6</italic>::<italic>RET</italic> and of <italic>NCOA4</italic>::<italic>RET</italic> were not significantly associated with clinicopathological data.</p><p><bold>Conclusion:</bold><italic>CCDC6</italic>::<italic>RET</italic> was correlated with an innocent PTC subtype and characteristics, but <italic>NCOA4</italic>::<italic>RET</italic> correlated with an aggressive phenotype of PTC. Therefore, these <italic>RET</italic> rearrangements strongly associated with clinicopathological phenotypes and can be used as predictive markers in PTC patients.</p>