Validation of molecular profiling to preoperatively predict aggressive pathologic features in differentiated thyroid...

Area of Science:

• Endocrinology
• Molecular Biology
• Oncology

Background:

• The American Thyroid Association (ATA) guidelines use pathology to stratify differentiated thyroid cancer recurrence risk.
• Aggressive features can reclassify tumors to intermediate-to-high risk, potentially necessitating completion thyroidectomy.
• Molecular expression profiles (signatures) may offer preoperative risk assessment to guide surgical decisions.

Purpose of the Study:

• To evaluate if molecular expression signatures can preoperatively differentiate high-risk thyroid tumors.
• To determine if these signatures can guide the extent of thyroid cancer surgery.

Main Methods:

• Retrospective analysis of 445 patients undergoing thyroid nodule molecular testing and resection (2017-2024).
• Patients categorized into ATA low-risk or intermediate/high-risk groups based on surgical pathology.
• Assessed 30 molecular signatures, including Invasion Score and Sodium-Iodide Symporter Expression, comparing expression between risk groups using statistical tests and logistic regression.

Main Results:

• Of 445 patients, 366 were low risk and 79 were intermediate/high risk.
• Twenty-three of 30 evaluated signatures showed significant expression variation between risk cohorts.
• Multivariate analysis identified Invasion Score as predictive of higher ATA risk (OR 1.3, P=.005) and Sodium-Iodide Symporter Expression as protective (OR 0.78, P=.015).

Conclusions:

• Multiple molecular signatures demonstrate significant variation across ATA risk classes, potentially improving preoperative prognostication.
• The Invasion Score signature correlates with aggressive pathologic features.
• Upregulated Sodium-Iodide Symporter Expression may indicate a lower risk profile, warranting further investigation.