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