NIS expression in thyroid tumors, relation with prognosis clinicopathological and molecular features

Area of Science:

• Molecular Oncology
• Thyroid Cancer Research
• Cancer Biomarkers

Background:

• Thyroid cancer treatment relies on surgery and radioiodine therapy.
• Radioiodine uptake by cancer cells depends on the sodium iodide symporter (NIS), encoded by the SLC5A5 gene, which must be targeted to the cell membrane.
• Understanding NIS expression's role in thyroid tumors is crucial for predicting treatment response and prognosis.

Purpose of the Study:

• To evaluate the utility of NIS expression in primary thyroid tumors for predicting tumor behavior, therapy response, and prognosis.
• To correlate SLC5A5 gene expression with clinicopathological features and genetic mutations in papillary thyroid carcinomas.

Main Methods:

• Quantitative real-time PCR (qPCR) and immunohistochemistry were used to assess NIS expression in primary thyroid tumors.
• SLC5A5 expression was analyzed in 378 primary papillary thyroid carcinomas from The Cancer Genome Atlas (TCGA) database for validation.
• Correlation analysis was performed between SLC5A5 expression, clinicopathological variables, and mutations in BRAF, RAS, and TERT promoter (TERTp).

Main Results:

• Lower SLC5A5 mRNA expression was associated with vascular invasion, extrathyroidal extension, and BRAFV600E mutation in the study series.
• TCGA data analysis confirmed these findings and revealed significantly lower SLC5A5 expression in larger tumors with recurrences, metastases, or RAS, BRAF, and/or TERTp mutations.
• Immunohistochemistry showed NIS membrane expression in only 12/211 cases, with variable therapeutic outcomes and mostly wild-type status for key mutations.

Conclusions:

• Reduced SLC5A5 mRNA expression is linked to aggressive thyroid cancer features and detrimental genetic alterations (BRAF, RAS, TERTp).
• Mutations in these genes appear to reduce NIS protein expression and its cell membrane targeting.
• SLC5A5 mRNA expression serves as a more informative biomarker for thyroid tumor aggressiveness and prognostic assessment compared to NIS immunohistochemical expression.