Prognostication with Thyroid GuidePx in the context of tall cell variants

Area of Science:

• Oncology
• Genomics
• Molecular Pathology

Background:

• The tall cell variant of papillary thyroid cancer (PTC) is associated with a poorer prognosis than the classical variant.
• Thyroid GuidePx is a genomic classifier that categorizes PTC into three molecular subtypes using fine-needle aspirate samples.
• Subtypes 1 and 2 generally exhibit low recurrence rates, particularly in early-stage tumors (1-4 cm and N0), while Type 3 is linked to aggressive behavior and high recurrence rates.

Purpose of the Study:

• To investigate the interaction between tall cell variant histology and the risk stratification provided by the Thyroid GuidePx classifier in papillary thyroid cancer.
• To evaluate the clinical implications of tall cell variant presence within different molecular subtypes and stages of PTC.

Main Methods:

• Gene expression data from 736 patients were analyzed using the Thyroid GuidePx classifier.
• Papillary thyroid cancer cases were classified as "early" (tumor size 1-4 cm and N0) or "advanced".
• Structural recurrence was the primary endpoint; transcriptomic and genomic analyses explored biological differences between tall cell variant and non-tall cell variant PTCs.

Main Results:

• Thyroid GuidePx classified 369 early PTCs into Type 1 (35%), Type 2 (45.5%), and Type 3 (19.5%), with recurrence rates of 3.9%, 1.9%, and 19.4%, respectively.
• Tall cell variants were uncommon in early Type 2 PTC (4.2%) but showed no recurrence; however, they were more frequent in advanced Type 2 PTC (10.2%, P=.04).
• In Type 3 PTC, tall cell variants showed significantly higher recurrence rates in advanced tumors (50% vs. 28.6% for non-tall cell variants, P=.01) and were associated with increased cell proliferation, invasion, and inflammation.

Conclusions:

• Thyroid GuidePx effectively identifies a low-risk subgroup (early Type 1 and Type 2 PTC) suitable for conservative management.
• Tall cell variants are rare in this low-risk group and did not recur; however, they appear to increase recurrence risk in Type 3 PTC, particularly in advanced stages.
• The study highlights the utility of genomic classification in refining risk assessment for papillary thyroid cancer, especially when considering specific histological variants like the tall cell type.