Low TPO-antibody titers appear to promote aggressive thyroid cancers tumorigenesis: analysis of a large multinational dataset

Rodis Paparodis; Evaggelos Karvounis; Aikaterini Kapezanou; Dimitra Bantouna; Sarantis Livadas; George Simeakis; Dimitrios Askitis; Ioannis Androulakis; Nicholas Angelopoulos; Dimitra Zianni; Ilias Perogamvros; Anastasios Boniakos; Andreas Rizoulis; Shanawaz Imam; Jaume Juan Carlos

doi:10.1530/endoabs.99.P155

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Endocrine Abstracts (2024) 99 P155 | DOI: 10.1530/endoabs.99.P155

ECE2024 Poster Presentations Thyroid (58 abstracts)

Low TPO-antibody titers appear to promote aggressive thyroid cancers tumorigenesis: analysis of a large multinational dataset

Rodis Paparodis ^1,2,3 , Evaggelos Karvounis ^1,4 , Aikaterini Kapezanou ⁴ , Dimitra Bantouna ¹ , Sarantis Livadas ^1,5 , George Simeakis ^1,6 , Dimitrios Askitis ^1,7 , Ioannis Androulakis ^1,8 , Nicholas Angelopoulos ^1,7 , Dimitra Zianni ^1,5 , Ilias Perogamvros ⁹ , Anastasios Boniakos ^1,5 , Andreas Rizoulis ¹⁰ , Shanawaz Imam ¹¹ & Juan Carlos Jaume ³

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¹Hellenic Endocrine Network, Athens, Greece; ²Endocrinology, Diabetes and Metabolism Clinics, Private Practice, Patras, Greece; ³Loyola University Medical Center / Edward Hines Jr VA Hospital, Maywood, IL, United States; ⁴Euroclinic Hospital, Center for Excellence in Edocrine Surgery, Athens, Greece; ⁵Endocrinology, Diabetes and Metabolism Clinics, Private Practice, Athens, Greece; ⁶401 General Military Hospital of Athens, Endocrine Deptartment Thyroid Cancer Outpatient’s Clinic, Athens, Greece; ⁷Endocrinology, Diabetes and Metabolism Clinics, Private Practice, Kavala, Greece; ⁸Endocrinology, Diabetes and Metabolism Clinics, Private Practice, Chania, Greece; ⁹University of Manchester, Manchester, United Kingdom; ¹⁰Endocrinology, Diabetes and Metabolism Clinics, Private Practice, Larisa, Greece; ¹¹University of Toledo College of Medicine and Life Sciences, Center for Diabetes and Endocrine Research, Toledo, OH, United States

Introduction: In the thyroid gland, humoral immunity manifests with thyroid peroxidase (TPO) antibodies. In our studies, when TPO concentrations increased, thyroid cancers of follicular origin (TCFO) tended to develop less frequently.¹ Other studies, though, reported an opposite trend in less aggressive cancers. The present work was designed to characterize the differential role of TPO antibodies in aggressive forms of TCFO (AGG) as compared to non-aggressive (NAG) ones.

Methods: We performed a retrospective review of data from subjects who had thyroidectomy at 4 centers, in 2 countries [USA: 1 (2007-2013) and Greece: 3 (2021-2023)] on gender, age, surgical pathology and preoperative TPO antibody concentrations. 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 were deemed AGG, while those not exhibiting these features were deemed NAG, and a control group was formed from subjects with benign histology (BEN). TPO were divided 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 ratios were compared between these subgroups.

Results: TPO titers were available for 1,943/11,212 subjects; n=948 BEN (48.8%). Overall mean age 46.7±14.9 years, lower in TCFO (45.7±14.6) compared to BEN (47.7±15.1), and in AGG (40.2±15.3) compared to non-AGG (46.2±14.5), P<0.01 for all comparisons. Overall n=1477 (76.0%) were females; 736/1477 (49.8%) with TCFO as compared to 259/466 (55.6%) in males, P=0.02. Out of 995 TCFO, n=73 (7.3%) were AGG. These were found more frequently in the VL (P=0.018) and less frequently in the H groups (P=0.016).

Conclusion: Patients with very low TPO titers harbor aggressive (AGG) thyroid cancers of follicular origin (TCFO) more commonly, while those with high titers harbor these more rarely. These findings imply that immune response in the form of TPO antibodies modulates the risk to develop aggressive thyroid cancers. A strong autoimmune response appears protective with regard to the development of aggressive tumors even though abnormal.

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.