TROP-2 and 5hmC expression in follicular-patterned thyroid neoplasm emphasizing tiny well-formed papillae.

Area of Science:

• Thyroid pathology
• Oncology
• Molecular diagnostics

Background:

• Follicular-patterned thyroid neoplasms (FPTNs) encompass diverse entities with predominantly follicular growth.
• Accurate classification is crucial for patient management and prognosis.
• Investigating nuclear features and specific biomarkers can aid in differentiating these neoplasms.

Purpose of the Study:

• To analyze nuclear characteristics and immunoexpression of TROP-2 and 5hmC in FPTNs.
• To correlate these findings with histological subtypes and clinical behavior.
• To refine diagnostic criteria for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

Main Methods:

• FPTNs were categorized into four groups based on histological features, including NIFTP, encapsulated FVPTC, infiltrative FVPTC, and PTC with follicular pattern and papillae.
• Quantitative image analysis assessed nuclear features.
• Immunohistochemistry evaluated TROP-2 and 5hmC expression, correlated with histological data using QuPath.

Main Results:

• A progressive increase in nuclear atypia (size, irregularity, chromatin clearing) was observed from NIFTP to advanced PTC.
• Trophoblast cell-surface antigen 2 (TROP-2) expression mirrored the trend of increasing nuclear atypia.
• 5-hydroxymethylcytosine (5hmC) expression was preserved in less advanced groups but significantly reduced in the most aggressive PTC group (Group IV), which also showed higher lymph node involvement and BRAF V600E mutation rates.

Conclusions:

• Group IV PTCs demonstrate the most significant nuclear atypia, highest TROP-2 expression, and substantial 5hmC loss.
• These findings reinforce the importance of excluding even minimal papillae (<1%) for NIFTP diagnosis.
• The study highlights the utility of TROP-2 and 5hmC as potential biomarkers in FPTN classification.