# Part 1: The Role of Thyroglobulin Antibodies in Thyroid Cancer Development and Aggressiveness

## TL;DR

A blood test measuring thyroglobulin antibodies may help predict lymph node metastasis in thyroid cancer, but not cancer development.

## Contribution

This study clarifies that thyroglobulin antibodies are linked to lymph node metastasis but not thyroid cancer incidence.

## Key findings

- Thyroglobulin antibodies were associated with increased likelihood of lymph node metastasis.
- Tumor aggressiveness features like capsular invasion were more common in antibody-positive patients.
- Thyroglobulin antibodies were not independently linked to thyroid cancer development.

## Abstract

In this study, we investigated the validity of a blood test to predict thyroid cancer presence and aggressiveness. The blood test measures antibodies raised against a thyroid protein, thyroglobulin. The results suggest that testing for the presence of thyroglobulin antibodies predicts the likelihood of metastasis to lymph nodes, a feature of cancer aggressiveness.

Introduction: Thyroglobulin antibodies (Tg-Abs) are often thought to be associated with thyroid autoimmunity, and as such, a link with thyroid cancer has been found in some, but not all, studies. Tg-Abs are also found in non-autoimmune thyroid-follicular destruction. Given these contradictory results, we designed the present study. Methods: We reviewed data from patients undergoing thyroidectomy for different indications in multiple centers across Greece and the US over 10 years. We compared the incidence of thyroid cancer and its features of tumor aggressiveness among patients with positive (≥30 IU/mL) and negative (<30 IU/mL) Tg-Abs titers and the Tg-Abs titers among patients with cancer, benign disease, and those with and without features of tumor aggressiveness. Furthermore, we performed multivariate and multiple regression analyses to identify if these effects were independently statistically significant. Results: We reviewed n = 9463 consecutive thyroidectomies and included n = 2873 subjects in the present work: n = 1537 with thyroid cancer and n = 1336 with benign disease. The incidence of thyroid cancer was significantly higher in preoperative Tg-Abs+ subjects, n = 273/638 (57.2%), compared with Tg-Abs− subjects, n = 1063/2235 (52.4%), OR 1.21, p < 0.05. Tumor size was larger, and capsular invasion and lymph node involvement were significantly more common in Tg-Abs+ subjects. Mean Tg-Abs were higher in subjects with tumors with extrathyroidal extension, capsular invasion, and lymph node involvement. On regression, Tg-Abs positivity was not associated with thyroid cancer incidence or aggressiveness, though, with the important exception of lymph node involvement (p < 0.001). Conclusions: Elevated preoperative thyroglobulin-antibody titers do not seem to affect the likelihood of developing thyroid cancer, even though they seem to be a surrogate for lymph node metastasis (as opposed to thyroid peroxidase antibodies, TPO-Abs). Further work is needed to clarify the interplay of this immune response on thyroid cancer metastatic behavior.