7144 Lack Of TPO Antibodies Heralds “Immune Escape” Of Aggressive Thyroid Cancers Of Follicular Origin: An International Retrospective Analysis Of 1,943 Consecutive Thyroidectomy Cases

Abstract Disclosure: R.D. Paparodis: None. E. Karvounis: None. A. Kapezanou: None. D. Bantouna: None. S. Livadas: None. G. Simeakis: None. D.P. Askitis: None. I. Androulakis: None. N.G. Angelopoulos: None. D. Zianni: None. I. Perogamvros: None. A. Boniakos: None. A. Rizoulis: None. S. Imam: None. J.C. Jaume: None. Introduction: Thyroid peroxidase (TPO) antibodies are a form of humoral immunity. We recently found that high TPO antibody titers tend to limit the expansion/progression of thyroid cancers of follicular origin (TCFO).[1] Many studies report the opposite trend, mostly for indolent TCFO. We designed the present study to assess whether TPO antibodies have differential effects on the expansion/progression of aggressive (AGG) as opposed to non-aggressive (NAG) TCFO. Methods: We collected data from patients that underwent thyroidectomies at 4 centers, in 2 countries [USA: 1 (2007-2013) and Greece: 3 (2021-2023)] on gender, age, surgical pathology and preoperative TPO antibody titers. We considered AGG thyroid cancers, those tumors producing distant metastases, spreading to multiple lymph nodes (LNs) (≥ 10 or ≥ 6 with a positive malignant to benign ratio ≥ 75%), those requiring ≥ 2 courses of I-131 therapy or large structural local recurrences. The remainder were considered NAG. Subjects with benign histology (BEN) served as controls. TPO antibody titers were grouped in very low (VL) (< 1 IU/ml), low (L) (1 - 10 IU/ml), intermediate (IN) (10 - 30 IU/ml), high (HI) (30-300 IU/ml) and very high (VH) (≥300 IU/ml). AGG thyroid cancer incidence was compared among different subgroups. Results: Out of 11,212 patients/operations reviewed, 1,943 subjects had available preoperative TPO antibody titers: n=995 (51.2%) with TCFO. The population's mean age was 46.7±14.9 years, significantly higher in BEN (47.7±15.1) compared to TCFO (45.7±14.6), and also higher in non-AGG (46.2±14.5), compared to the AGG (40.2±15.3), p<0.01 for all comparisons. Overall n=466 (24.0%) were males; 259/466 with TCFO (55.6%), significantly higher compared to the 736/1487 (49.5%) in females (p=0.02). Based on the above criteria, AGG were n=73/995 (7.3%) and were significantly more common in VL (p=0.018) and less common in H (p=0.016) (see table). Conclusions: Aggressive (AGG) thyroid cancers of follicular origin (TCFO) are more commonly found in patients with very low and more rarely in those with high TPO antibody titers. Our findings imply that aggressive thyroid cancers can escape immunity. An intact humoral, albeit autoimmune, response seems protective in that regard. Reference: [1] Paparodis R, Livadas S, Karvounis E, Bantouna D, Zoupas I, Angelopoulos N, Imam S, Jaume JC. Elevated Preoperative TPO Ab Titers Decrease Risk for DTC in a Linear Fashion: A Retrospective Analysis of 1635 Cases. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e347-e355. doi: 10.1210/clinem/dgad408. PMID: 37440589. Presentation: 6/2/2024