ETA2024 Oral Presentations Oral Session 6: Translational thyroid cancer research (7 abstracts)
The role of TPO antibodies in immune escape of aggressive tumors of thyroid follicular cells
Rodis Paparodis 1 , Evangelos Karvounis 2 , Aikaterini Kapezanou 2 , Dimitra Bantouna 3 , Sarantis Livadas 4 , George Simeakis 5 , Dimitrios Askitis 6 , Ioannis Androulakis 7 , Nikolas Angelopoulos 8 , Dimitra Zianni 4 , Ilias Perogamvros 9 , Anastasios Boniakos 4 , Andreas Rizoulis 10 , Shahnawaz Imam 11 & Juan Jaume 12
1Helenic Endocrine Network, Endocrinology, Diabetes and Metabolism, Patras, Greece; 2Euroclinic Hospital, Endocrine Surgery Center of Excellence, Athens, Greece; 3Hellenic Endocrine Network, Patras, Greece; 4Hellenic Endocrine Network, Athens, Greece; 5401 General Military Hospital of Athens, Endocrine Dept - Thyroid Cancer Outpatient Clinic, Athens, Greece; 6Private Practice for Endocrinology, Alexandroupolis, Greece; 7Private Practice, Pvt, Chania, Greece; 8Hellenic Endocrine Network, Kavala, Greece; 9University of Manchester, Manchester, United Kingdom; 10Hellenic Endocrine Network, Larisa, Greece; 11University of Toledo College of Medicine and Life Sciences, Center for Diabetes and Endocrine Research, Toledo, Oh, United States; 12Loyola University Medical Center/Edward Hines Jr Va Hospital, Endocrinology, Diabetes and Metabolism, Hines, Il, United States
Introduction: Our previous observations suggested that high titers TPO antibodies titers limit the extent of differentiated thyroid cancer.1 Other studies found an opposite effect, especially when it comes to indolent tumors. 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) tumors of follicular cells origin (TCFO).
Methods: For the present work we gathered data from thyroid surgeries performed at four centers, in two countries [USA: 1 (2007-2013) and Greece: 3 (2021-2023)] on gender, age, surgical pathology and preoperative TPO antibody titers. AGG thyroid cancers were deemed 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 five categories: 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: We reviewed a total of 11,212 surgeries and 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 higher in non-AGG (46.2±14.5), compared to the AGG (40.2±15.3) subgroup, P < 0.01 for all comparisons. Overall n = 1477 (76.0%) were females; 736/1487 (49.5%) with TCFO, which was significantly lower compared to the 55.6% (259/466) found in males, (P = 0.02). Based on the above criteria, AGG were significantly more common in VL (P = 0.018) and less common in H (P = 0.016) patients’ subgroups (see table).
| TPO Ab Titer | BEN | DTC | NON-AGG | AGG | Total |
| VL (≤ 1) | 308 (32.2%) | 285 (28.6%) | 347 (37.6%) | 38 (52.1%) | 693 |
| L (1-10) | 106 (11.1%) | 99 (9.9%) | 95 (10.3%) | 4 (5.5%) | 205 |
| INT (10-30) | 208 (21.7%) | 210 (21.1%) | 195 (21.1%) | 15 (20.9%) | 418 |
| HI (30-300) | 190 (19.8%) | 199 (20.0%) | 192 (20.8%) | 7 (9.6%) | 389 |
| VH (>300) | 146 (15.2%) | 102 (10.3%) | 93 (10.1%) | 9 (12.3%) | 248 |
| Total | 958 | 995 | 922 | 73 | 1943 |
Conclusions: Aggressive forms of thyroid cancers are more commonly found in patients with very low and more rarely in those with high TPO antibody titers. Our findings imply that the lack of TPO antibodies in aggressive thyroid cancers is a means of immunity escape. 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 Riskfor 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.
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