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Revised Thyroid Differentiation Score for Risk Stratification in Papillary Thyroid Carcinoma
Vicente R Marczyk1,2, Chia Chin Wu1, Sarah Hamidi2
1Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX.
JCO Precision Oncology
|July 23, 2026
Summary
A new scoring system, xTDS, reliably measures thyroid tumor differentiation. This improved method is reproducible and predicts patient outcomes, offering clinical value for aggressive papillary thyroid cancers.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Papillary thyroid carcinomas (PTCs) can exhibit aggressive behavior due to loss of thyroid differentiation.
- The Cancer Genome Atlas (TCGA) developed the Thyroid Differentiation Score (TDS) to quantify tumor differentiation, but it lacks reproducibility and clinical utility.
Purpose of the Study:
- To develop and validate a revised Thyroid Differentiation Score (xTDS) for reproducible assessment of tumor differentiation in PTC.
- To evaluate the prognostic relevance of xTDS across independent patient cohorts.
Main Methods:
- RNA sequencing data from 570 PTC patients across three cohorts (MD Anderson, Vanderbilt, TCGA) were analyzed.
- The revised score (xTDS) was assessed for correlation with the original TDS, association with oncogenic drivers (BRAF, RAS), and prognostic value for disease-specific survival (DSS) and progression-free survival (PFS).
Main Results:
- xTDS demonstrated near-perfect correlation with the original TDS (Spearman ρ = 0.98).
- Tumors with BRAF V600E mutations showed lower differentiation scores, while RAS-driven tumors had higher scores (P < .001).
- Low xTDS was significantly associated with worse DSS and PFS across multiple cohorts, indicating prognostic value.
Conclusions:
- The xTDS is a reproducible and clinically relevant measure of thyroid tumor differentiation.
- xTDS overcomes the technical limitations of the original TDS while retaining its biological and prognostic significance.
- This validated score can aid in assessing PTC aggressiveness and patient prognosis.
